rewirebio.iobenchmarks

Use caseProteins and complexesResearch only

Predict missense variant effects in a protein of interest

Which predictor best ranks the functional effects of amino acid substitutions in a given protein, with or without an alignment or structure?

You bring
  • Wild-type protein sequence and the substitutions to score
  • Optionally a multiple sequence alignment, an experimental or predicted structure, and labelled assay data
  • The readout of interest (activity, binding, expression, stability or organismal fitness)
You want
Per-predictor rank correlation with deep mutational scanning readouts across many proteins, with breakdowns by alignment depth, function type and taxon, and pairwise win rates on human proteins. No guarantee for a specific protein.
Evidence in this release
2 comparisons shown · 115 tools · 194 configurations
Kept up to date
Evidence last checked 14 October 2026 · re-checked monthly, next due 14 November 2026

Baseline

Site-independent alignment model. An alignment-based model that scores each position separately, without the dependencies between positions that EVmutation adds, and with no neural network. It is the first and simplest model in the ProteinGym substitution baselines table (input modality MSA; Hopf et al. 2017).

Machine-learning methods are compared with the baseline on the same data in one table: ProteinGym zero-shot DMS substitutions (commit 144fe22). Baseline rows are marked in each table.

Tools compared

Comparisons

Each table is one study or protocol with its own truth set and scoring. Compare tools within a table, not across tables.

Livesey and Marsh 2025 VEP rankings

Direct evidenceIndependent study

Pairwise win rate (higher is better), with the other metrics below each value. Showing the top 10 of 97 rows. The best value in each column is highlighted.

Scroll sideways to see all 5 columns.

ToolDMS benchmark, all 36 DMS setsDMS benchmark, direct assays onlyDMS benchmark, indirect assays onlyDMS benchmark, SNV-accessible substitutionsDMS benchmark, SNV-accessible, gaps filled
CPT-1machine learning92.82% (best in column)all other VEPs,Pairwise win rate 66.2%93.46% (best in column)92.08% (best in column)92.13% (best in column)91.91% (best in column)
AlphaMissensemachine learning90.69%all other VEPs,Pairwise win rate 65.3%92.14%89.50%89.20%89.46%
ESCOTTspecialist model88.18%all other VEPs,Pairwise win rate 50.7%91.77%85.51%87.27%87.09%
popEVEspecialist model87.27%all other VEPs,Pairwise win rate 46.3%89.19%86.10%87.89%88.12%
iGEMMEspecialist model86.02%all other VEPs,Pairwise win rate 34.9%89.59%83.41%85.94%85.81%
GEMMEspecialist model84.94%all other VEPs,Pairwise win rate 36.1%88.70%82.15%83.61%83.78%
SaProtfoundation model83.56%all other VEPs,Pairwise win rate 45.2%84.80%82.72%83.39%83.22%
TranceptEVEspecialist model82.08%all other VEPs,Pairwise win rate 25.7%88.50%78.18%83.60%75.21%
VARITY_Rmachine learning81.84%all other VEPs,Pairwise win rate 31.8%77.52%86.41%81.84%82.07%
ESM-1vfoundation model81.49%all other VEPs,Pairwise win rate 28.1%78.36%83.63%81.52%81.83%
VARITY_ERmachine learning80.49%all other VEPs,Pairwise win rate 27.9%77.41%83.67%80.49%80.55%
mvPPTmachine learning77.72%all other VEPs,Pairwise win rate 24.5%73.95%82.13%77.72%70.86%
SNPredmachine learning77.57%all other VEPs,Pairwise win rate 20.8%79.06%76.39%77.57%78.13%
EVEspecialist model77.31%all other VEPs,Pairwise win rate 18.1%82.98%72.47%77.68%72.48%
DeepSequencespecialist model76.57%all other VEPs,Pairwise win rate 17.3%73.48%78.36%78.37%77.51%
CARPfoundation model76.05%all other VEPs,Pairwise win rate 20.0%73.05%77.69%77.16%71.21%
MSA_Transformerfoundation model75.89%all other VEPs,Pairwise win rate 24.4%77.72%74.67%79.24%71.98%
MetaRNNmachine learning73.20%all other VEPs,Pairwise win rate 16.6%74.83%71.86%73.20%74.07%
ESM2foundation model72.22%all other VEPs,Pairwise win rate 27.8%74.21%70.77%70.55%71.07%
MutFormermachine learning71.39%all other VEPs,Pairwise win rate 17.2%74.66%68.92%71.39%70.47%
VESPAmachine learning71.33%all other VEPs,Pairwise win rate 17.3%69.53%72.57%69.48%64.84%
EVmutation_epistaticspecialist model70.82%all other VEPs,Pairwise win rate 10.7%74.27%68.26%71.99%68.81%
PHACTboostmachine learning70.69%all other VEPs,Pairwise win rate 15.3%66.84%73.43%71.87%72.51%
gMVPmachine learning69.88%all other VEPs,Pairwise win rate 23.3%61.74%75.66%69.88%70.97%
mutationTCNspecialist model67.99%all other VEPs,Pairwise win rate 9.21%70.73%65.29%67.85%63.44%
UNEECONspecialist model66.79%all other VEPs,Pairwise win rate 12.5%68.09%65.67%66.79%65.15%
REVELmachine learning66.13%all other VEPs,Pairwise win rate 13.2%65.58%66.33%66.13%67.45%
ESM-1bfoundation model65.04%all other VEPs,Pairwise win rate 14.7%62.38%66.95%64.51%65.92%
EVmutation_independentspecialist model64.45%all other VEPs,Pairwise win rate 8.62%67.11%62.42%64.04%63.76%
MutScoremachine learning63.41%all other VEPs,Pairwise win rate 8.64%61.53%64.82%63.41%63.22%
ClinPredmachine learning63.16%all other VEPs,Pairwise win rate 4.36%66.86%60.42%63.16%64.48%
DEOGEN2machine learning59.39%all other VEPs,Pairwise win rate 11.4%66.07%54.64%59.84%61.09%
VEST4machine learning59.03%all other VEPs,Pairwise win rate 2.33%59.86%58.44%59.04%60.51%
MutationAssessorspecialist model58.80%all other VEPs,Pairwise win rate 10.3%59.34%58.32%58.80%57.31%
SNAP2machine learning58.66%all other VEPs,Pairwise win rate 7.84%56.53%59.94%56.98%58.32%
SuSPectmachine learning58.36%all other VEPs,Pairwise win rate 10.4%59.53%57.49%55.62%56.59%
SNPs&GOmachine learning57.38%all other VEPs,Pairwise win rate 5.91%54.96%59.04%59.02%54.23%
BayesDel_noAFmachine learning57.10%all other VEPs,Pairwise win rate 6%56.63%57.42%57.10%58.25%
BayesDelmachine learning56.92%all other VEPs,Pairwise win rate 5.44%56.77%57.01%56.92%58.13%
ProGen2foundation model56.66%all other VEPs,Pairwise win rate 8.89%60.96%53.06%56.51%58.58%
PHACTspecialist model54.74%all other VEPs,Pairwise win rate 6.71%51.62%56.96%55.24%56.41%
MISTICmachine learning54.51%all other VEPs,Pairwise win rate 7.24%57.28%52.33%54.51%55.43%
SPRImachine learning54.25%all other VEPs,Pairwise win rate 2%60.21%50.25%56.26%60.61%
MOIpred_benignmachine learning54.10%all other VEPs,Pairwise win rate 11.2%54.63%53.69%54.10%52.66%
DeepSAVmachine learning53.68%all other VEPs,Pairwise win rate 6.74%54.71%52.89%53.62%55.51%
MPCmachine learning53.56%all other VEPs,Pairwise win rate 11.6%57.19%50.68%53.56%54.78%
VESPAlmachine learning53.47%all other VEPs,Pairwise win rate 10.9%48.83%56.61%51.64%52.53%
Rhapsodymachine learning53.40%all other VEPs,Pairwise win rate 4.83%47.19%57.85%51.21%56.89%
PhD_SNPmachine learning53.35%all other VEPs,Pairwise win rate 1.99%52.24%54.01%55.62%50.74%
Eigenspecialist model52.37%all other VEPs,Pairwise win rate 4.83%53.68%51.30%52.37%53.87%
SIFT4Gconventional52.16%all other VEPs,Pairwise win rate 6.85%49.94%53.64%52.16%53.62%
DeMaSkmachine learning50.68%all other VEPs,Pairwise win rate 11.1%47.93%53.25%49.24%49.84%
PolyPhen2_HumVarmachine learning48.35%all other VEPs,Pairwise win rate 8.47%46.24%49.95%48.41%49.67%
PROVEANconventional48.07%all other VEPs,Pairwise win rate 5.47%50.96%45.97%48.28%49.99%
MutPredmachine learning47.95%all other VEPs,Pairwise win rate 14.4%46.47%49.04%47.95%49.24%
CONDELspecialist model47.52%all other VEPs,Pairwise win rate 9.76%45.21%49.04%47.52%47.78%
SNPs&GO3Dmachine learning47.51%all other VEPs,Pairwise win rate 7.16%44.78%49.44%47.68%47.46%
RITAfoundation model46.42%all other VEPs,Pairwise win rate 5.80%48.23%45.37%45.21%42.63%
SIGMAmachine learning46.13%all other VEPs,Pairwise win rate 10.6%47.69%45.16%46.13%47.10%
MetaLRmachine learning45.70%all other VEPs,Pairwise win rate 8.13%42.05%48.26%45.70%46.62%
Envisionmachine learning45.23%all other VEPs,Pairwise win rate 7.44%49.23%42.40%45.64%46.81%
Tranceptionfoundation model44.51%all other VEPs,Pairwise win rate 6.44%51.89%39.26%45.15%46.56%
PANTHERspecialist model44.42%all other VEPs,Pairwise win rate 1.86%44.14%44.57%45.68%37.66%
Wavenetspecialist model42.79%all other VEPs,Pairwise win rate 11.1%43.33%42.41%42.77%43.08%
LASSIEspecialist model42.67%all other VEPs,Pairwise win rate 1.22%45.21%40.97%42.67%43.78%
PolyPhen2_HumDivmachine learning42.41%all other VEPs,Pairwise win rate 6.76%41.50%43.11%42.41%44.12%
Maverick_benignmachine learning41.20%all other VEPs,Pairwise win rate 6.78%41.09%41.31%41.20%42.66%
Unirep_evotunefoundation model40.99%all other VEPs,Pairwise win rate 2.86%37.68%42.93%40.82%38.99%
CADD_1.7machine learning40.32%all other VEPs,Pairwise win rate 2.89%38.96%41.24%40.32%41.99%
M-CAPmachine learning40.05%all other VEPs,Pairwise win rate 7.71%38.30%41.23%40.05%39.73%
SIFTconventional39.27%all other VEPs,Pairwise win rate 1.22%39.94%38.76%40.34%41.84%
MetaSVMmachine learning38.99%all other VEPs,Pairwise win rate 8.13%39.40%38.54%38.99%39.91%
MVPmachine learning36.36%all other VEPs,Pairwise win rate 5.36%31.32%39.93%36.36%37.77%
CADD_1.6machine learning34.99%all other VEPs,Pairwise win rate 1.22%34.41%35.38%35.05%36.95%
AlphScoremachine learning33.46%all other VEPs,Pairwise win rate 11.0%32.27%34.31%33.46%34.70%
CAPICEmachine learning29.43%all other VEPs,Pairwise win rate 3.69%29.09%29.67%29.43%30.05%
PonP2machine learning28.21%all other VEPs,Pairwise win rate 1.22%29.98%26.93%28.85%26.66%
InMeRFmachine learning27.01%all other VEPs,Pairwise win rate 4.11%26.03%27.77%27.01%28.33%
FathmmXFmachine learning24.52%all other VEPs,Pairwise win rate 1.83%27.15%22.57%24.52%25.52%
LIST-S2specialist model22.09%all other VEPs,Pairwise win rate 4.4%16.75%26.21%22.09%23.55%
sequence_unetspecialist model20.27%all other VEPs,Pairwise win rate 1.22%20.26%20.33%20.04%20.96%
PrimateAImachine learning19.93%all other VEPs,Pairwise win rate 1.22%17.48%21.69%19.93%20.96%
PhD-SNPgmachine learning18.92%all other VEPs,Pairwise win rate 0.667%20.11%18.11%18.92%20.39%
fathmm-MKLmachine learning16.14%all other VEPs,Pairwise win rate 0.667%15.80%16.33%16.14%17.09%
phyloPspecialist model15.41%all other VEPs,Pairwise win rate 0.667%17.71%13.78%15.41%16.70%
BLOSUM62conventional14.87%all other VEPs,Pairwise win rate 1.11%13.74%15.68%14.68%15.55%
FATHMMspecialist model14.62%all other VEPs,Pairwise win rate 2.33%12.66%16.05%14.32%15.31%
LRTspecialist model13.58%all other VEPs,Pairwise win rate 1.22%15.39%12.31%13.58%14.32%
DANNmachine learning13.40%all other VEPs,Pairwise win rate 0.667%14.51%12.62%13.40%14.51%
ProtGPT2foundation model11.80%all other VEPs,Pairwise win rate 0%8.46%14.32%11.06%11.09%
GenoCanyonspecialist model9.05%all other VEPs,Pairwise win rate 1.22%8.65%9.35%9.05%9.87%
GERP++specialist model8.80%all other VEPs,Pairwise win rate 0.667%9.13%8.55%8.80%9.43%
Granthamspecialist model8.78%all other VEPs,Pairwise win rate 0%7.32%9.79%9.13%10.03%
SiPhyspecialist model7.48%all other VEPs,Pairwise win rate 0%8.13%7.01%7.48%8.32%
3Cnetmachine learning7.05%all other VEPs,Pairwise win rate 0%3.51%9.57%6.37%6.65%
phastConsspecialist model7.01%all other VEPs,Pairwise win rate 0.667%9.13%5.50%7.01%7.54%
fitConsspecialist model6.51%all other VEPs,Pairwise win rate 3.12%2.48%9.52%6.51%6.66%
Show all 97 rowsShow the top 10 rows only
Caveats and method

What each column measures:

  • DMS benchmark, all 36 DMS sets: Average pairwise win rate of each missense VEP against 96 others, by |Spearman| with 36 human DMS datasets
  • DMS benchmark, direct assays only: Average pairwise win rate by |Spearman| with the DMS assays the authors class as direct
  • DMS benchmark, indirect assays only: Average pairwise win rate by |Spearman| with the DMS assays the authors class as indirect
  • DMS benchmark, SNV-accessible substitutions: Average pairwise win rate by |Spearman| restricted to substitutions reachable by one nucleotide change
  • DMS benchmark, SNV-accessible, gaps filled: Average pairwise win rate by |Spearman| on SNV-accessible substitutions with missing predictions set to each VEP's most benign score
  • DMS phenotypes are chosen per protein and are not pathogenicity labels.
  • Rank scores are relative to the VEP set compared; they are not a correlation and cannot be compared with other tables.
  • Human proteins only (36 DMS sets, one per protein).
  • Five VEPs were trained on DMS data (Envision, CPT-1, DeMaSk, VARITY_R, VARITY_ER); the authors excluded their results for the proteins used to train them (Table S2), but other methods may have been tuned against DMS data without direct training, for example ESM-1v's model selection (Results, Discussion).
  • Per-protein correlations are in the figshare deposit, not retrieved; averages do not predict a single protein.
  • Transcribed from the source; no reproduction by Rewire and no human scientific review.
  • Which assays are direct is not fully recoverable from Table S1 (four blank assay descriptions).
  • Which assays are indirect is not fully recoverable from Table S1.

Protocols: Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS sets, Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays only, Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays only, Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions only, Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filled

ProteinGym zero-shot DMS substitutions (commit 144fe22)

Direct evidenceOrigin not reported

Average_Spearman: mean over proteins of assay-level Spearman correlation between zero-shot scores and DMS readouts, 217 substitution assays, with breakdowns by MSA depth, function type, taxon and mutational depth

Spearman (higher is better), with the other metrics below each value. Showing the top 10 of 97 rows. The best value in each column is highlighted.

ToolAll assays (Average_Spearman) and breakdowns
AIDO Protein-RAG (16B)foundation model0.518 (best in column)mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.527Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.414Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.419Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.394
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.414Spearman (Activity assays: mean over proteins) 0.517Spearman (Binding assays: mean over proteins) 0.426Spearman (Expression assays: mean over proteins) 0.522Spearman (Organismal fitness assays: mean over proteins) 0.491Spearman (Stability assays: mean over proteins) 0.635Spearman (High MSA depth proteins: mean over proteins) 0.585Spearman (Low MSA depth proteins: mean over proteins) 0.498Spearman (Medium MSA depth proteins: mean over proteins) 0.534Spearman (Human proteins: mean over proteins) 0.531Spearman (Other eukaryote proteins: mean over proteins) 0.587Spearman (Prokaryote proteins: mean over proteins) 0.558Spearman (Virus proteins: mean over proteins) 0.522
VenusREMfoundation model0.518 (best in column)mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.534Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.397Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.355Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.322
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.368Spearman (Activity assays: mean over proteins) 0.495Spearman (Binding assays: mean over proteins) 0.454Spearman (Expression assays: mean over proteins) 0.533Spearman (Organismal fitness assays: mean over proteins) 0.459Spearman (Stability assays: mean over proteins) 0.65Spearman (High MSA depth proteins: mean over proteins) 0.577Spearman (Low MSA depth proteins: mean over proteins) 0.495Spearman (Medium MSA depth proteins: mean over proteins) 0.524Spearman (Human proteins: mean over proteins) 0.529Spearman (Other eukaryote proteins: mean over proteins) 0.582Spearman (Prokaryote proteins: mean over proteins) 0.549Spearman (Virus proteins: mean over proteins) 0.492
ProSST (K=2048)foundation model0.507mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.521Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.394Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.317Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.277
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.332Spearman (Activity assays: mean over proteins) 0.476Spearman (Binding assays: mean over proteins) 0.445Spearman (Expression assays: mean over proteins) 0.53Spearman (Organismal fitness assays: mean over proteins) 0.431Spearman (Stability assays: mean over proteins) 0.653Spearman (High MSA depth proteins: mean over proteins) 0.58Spearman (Low MSA depth proteins: mean over proteins) 0.465Spearman (Medium MSA depth proteins: mean over proteins) 0.507Spearman (Human proteins: mean over proteins) 0.516Spearman (Other eukaryote proteins: mean over proteins) 0.573Spearman (Prokaryote proteins: mean over proteins) 0.549Spearman (Virus proteins: mean over proteins) 0.454
ProSST (K=4096)foundation model0.498mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.505Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.426Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.388Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.342
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.408Spearman (Activity assays: mean over proteins) 0.444Spearman (Binding assays: mean over proteins) 0.472Spearman (Expression assays: mean over proteins) 0.507Spearman (Organismal fitness assays: mean over proteins) 0.416Spearman (Stability assays: mean over proteins) 0.652Spearman (High MSA depth proteins: mean over proteins) 0.583Spearman (Low MSA depth proteins: mean over proteins) 0.472Spearman (Medium MSA depth proteins: mean over proteins) 0.481Spearman (Human proteins: mean over proteins) 0.497Spearman (Other eukaryote proteins: mean over proteins) 0.574Spearman (Prokaryote proteins: mean over proteins) 0.547Spearman (Virus proteins: mean over proteins) 0.44
S3F-MSAfoundation model0.496mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.499Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.333Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.378Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.346
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.383Spearman (Activity assays: mean over proteins) 0.502Spearman (Binding assays: mean over proteins) 0.44Spearman (Expression assays: mean over proteins) 0.479Spearman (Organismal fitness assays: mean over proteins) 0.477Spearman (Stability assays: mean over proteins) 0.581Spearman (High MSA depth proteins: mean over proteins) 0.547Spearman (Low MSA depth proteins: mean over proteins) 0.469Spearman (Medium MSA depth proteins: mean over proteins) 0.509Spearman (Human proteins: mean over proteins) 0.502Spearman (Other eukaryote proteins: mean over proteins) 0.558Spearman (Prokaryote proteins: mean over proteins) 0.521Spearman (Virus proteins: mean over proteins) 0.502
S2F-MSAfoundation model0.488mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.491Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.303Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.346Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.318
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.362Spearman (Activity assays: mean over proteins) 0.498Spearman (Binding assays: mean over proteins) 0.432Spearman (Expression assays: mean over proteins) 0.472Spearman (Organismal fitness assays: mean over proteins) 0.472Spearman (Stability assays: mean over proteins) 0.567Spearman (High MSA depth proteins: mean over proteins) 0.536Spearman (Low MSA depth proteins: mean over proteins) 0.463Spearman (Medium MSA depth proteins: mean over proteins) 0.502Spearman (Human proteins: mean over proteins) 0.495Spearman (Other eukaryote proteins: mean over proteins) 0.546Spearman (Prokaryote proteins: mean over proteins) 0.513Spearman (Virus proteins: mean over proteins) 0.493
ProSST (K=1024)foundation model0.485mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.492Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.434Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.373Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.341
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.403Spearman (Activity assays: mean over proteins) 0.433Spearman (Binding assays: mean over proteins) 0.436Spearman (Expression assays: mean over proteins) 0.499Spearman (Organismal fitness assays: mean over proteins) 0.414Spearman (Stability assays: mean over proteins) 0.642Spearman (High MSA depth proteins: mean over proteins) 0.585Spearman (Low MSA depth proteins: mean over proteins) 0.457Spearman (Medium MSA depth proteins: mean over proteins) 0.466Spearman (Human proteins: mean over proteins) 0.483Spearman (Other eukaryote proteins: mean over proteins) 0.568Spearman (Prokaryote proteins: mean over proteins) 0.539Spearman (Virus proteins: mean over proteins) 0.436
Protrieverfoundation model0.479mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.473Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.32Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.427Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.387
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.427Spearman (Activity assays: mean over proteins) 0.487Spearman (Binding assays: mean over proteins) 0.396Spearman (Expression assays: mean over proteins) 0.496Spearman (Organismal fitness assays: mean over proteins) 0.479Spearman (Stability assays: mean over proteins) 0.537Spearman (High MSA depth proteins: mean over proteins) 0.512Spearman (Low MSA depth proteins: mean over proteins) 0.464Spearman (Medium MSA depth proteins: mean over proteins) 0.498Spearman (Human proteins: mean over proteins) 0.48Spearman (Other eukaryote proteins: mean over proteins) 0.542Spearman (Prokaryote proteins: mean over proteins) 0.492Spearman (Virus proteins: mean over proteins) 0.516
ESCOTT0.476mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.476Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.314Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.377Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.385
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.434Spearman (Activity assays: mean over proteins) 0.499Spearman (Binding assays: mean over proteins) 0.389Spearman (Expression assays: mean over proteins) 0.468Spearman (Organismal fitness assays: mean over proteins) 0.466Spearman (Stability assays: mean over proteins) 0.557Spearman (High MSA depth proteins: mean over proteins) 0.524Spearman (Low MSA depth proteins: mean over proteins) 0.462Spearman (Medium MSA depth proteins: mean over proteins) 0.496Spearman (Human proteins: mean over proteins) 0.486Spearman (Other eukaryote proteins: mean over proteins) 0.537Spearman (Prokaryote proteins: mean over proteins) 0.5Spearman (Virus proteins: mean over proteins) 0.502
ProSST (K=512)foundation model0.471mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.476Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.41Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.354Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.314
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.383Spearman (Activity assays: mean over proteins) 0.423Spearman (Binding assays: mean over proteins) 0.431Spearman (Expression assays: mean over proteins) 0.479Spearman (Organismal fitness assays: mean over proteins) 0.394Spearman (Stability assays: mean over proteins) 0.629Spearman (High MSA depth proteins: mean over proteins) 0.572Spearman (Low MSA depth proteins: mean over proteins) 0.437Spearman (Medium MSA depth proteins: mean over proteins) 0.451Spearman (Human proteins: mean over proteins) 0.472Spearman (Other eukaryote proteins: mean over proteins) 0.55Spearman (Prokaryote proteins: mean over proteins) 0.529Spearman (Virus proteins: mean over proteins) 0.408
PoET (200M)foundation model0.470mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.466Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.299Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.419Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.395
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.418Spearman (Activity assays: mean over proteins) 0.494Spearman (Binding assays: mean over proteins) 0.396Spearman (Expression assays: mean over proteins) 0.466Spearman (Organismal fitness assays: mean over proteins) 0.475Spearman (Stability assays: mean over proteins) 0.519Spearman (High MSA depth proteins: mean over proteins) 0.51Spearman (Low MSA depth proteins: mean over proteins) 0.478Spearman (Medium MSA depth proteins: mean over proteins) 0.478Spearman (Human proteins: mean over proteins) 0.482Spearman (Other eukaryote proteins: mean over proteins) 0.541Spearman (Prokaryote proteins: mean over proteins) 0.464Spearman (Virus proteins: mean over proteins) 0.491
S3Ffoundation model0.470mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.485Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.328Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.331Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.293
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.337Spearman (Activity assays: mean over proteins) 0.468Spearman (Binding assays: mean over proteins) 0.404Spearman (Expression assays: mean over proteins) 0.472Spearman (Organismal fitness assays: mean over proteins) 0.413Spearman (Stability assays: mean over proteins) 0.594Spearman (High MSA depth proteins: mean over proteins) 0.551Spearman (Low MSA depth proteins: mean over proteins) 0.42Spearman (Medium MSA depth proteins: mean over proteins) 0.471Spearman (Human proteins: mean over proteins) 0.486Spearman (Other eukaryote proteins: mean over proteins) 0.536Spearman (Prokaryote proteins: mean over proteins) 0.512Spearman (Virus proteins: mean over proteins) 0.415
ProSST (K=128)foundation model0.469mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.472Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.418Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.376Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.332
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.394Spearman (Activity assays: mean over proteins) 0.417Spearman (Binding assays: mean over proteins) 0.44Spearman (Expression assays: mean over proteins) 0.473Spearman (Organismal fitness assays: mean over proteins) 0.387Spearman (Stability assays: mean over proteins) 0.628Spearman (High MSA depth proteins: mean over proteins) 0.566Spearman (Low MSA depth proteins: mean over proteins) 0.441Spearman (Medium MSA depth proteins: mean over proteins) 0.447Spearman (Human proteins: mean over proteins) 0.466Spearman (Other eukaryote proteins: mean over proteins) 0.545Spearman (Prokaryote proteins: mean over proteins) 0.523Spearman (Virus proteins: mean over proteins) 0.415
ESM3 open (1.4B)foundation model0.466mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.487Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.337Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.307Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.285
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.363Spearman (Activity assays: mean over proteins) 0.43Spearman (Binding assays: mean over proteins) 0.4Spearman (Expression assays: mean over proteins) 0.47Spearman (Organismal fitness assays: mean over proteins) 0.389Spearman (Stability assays: mean over proteins) 0.641Spearman (High MSA depth proteins: mean over proteins) 0.575Spearman (Low MSA depth proteins: mean over proteins) 0.397Spearman (Medium MSA depth proteins: mean over proteins) 0.466Spearman (Human proteins: mean over proteins) 0.48Spearman (Other eukaryote proteins: mean over proteins) 0.548Spearman (Prokaryote proteins: mean over proteins) 0.53Spearman (Virus proteins: mean over proteins) 0.406
RSALOR0.465mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.474Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.292Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.369Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.392
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.453Spearman (Activity assays: mean over proteins) 0.479Spearman (Binding assays: mean over proteins) 0.416Spearman (Expression assays: mean over proteins) 0.427Spearman (Organismal fitness assays: mean over proteins) 0.426Spearman (Stability assays: mean over proteins) 0.575Spearman (High MSA depth proteins: mean over proteins) 0.529Spearman (Low MSA depth proteins: mean over proteins) 0.467Spearman (Medium MSA depth proteins: mean over proteins) 0.468Spearman (Human proteins: mean over proteins) 0.473Spearman (Other eukaryote proteins: mean over proteins) 0.53Spearman (Prokaryote proteins: mean over proteins) 0.496Spearman (Virus proteins: mean over proteins) 0.477
VespaGmachine learning0.458mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.456Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.247Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.346Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.323
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.367Spearman (Activity assays: mean over proteins) 0.493Spearman (Binding assays: mean over proteins) 0.37Spearman (Expression assays: mean over proteins) 0.456Spearman (Organismal fitness assays: mean over proteins) 0.437Spearman (Stability assays: mean over proteins) 0.533Spearman (High MSA depth proteins: mean over proteins) 0.511Spearman (Low MSA depth proteins: mean over proteins) 0.427Spearman (Medium MSA depth proteins: mean over proteins) 0.472Spearman (Human proteins: mean over proteins) 0.474Spearman (Other eukaryote proteins: mean over proteins) 0.532Spearman (Prokaryote proteins: mean over proteins) 0.484Spearman (Virus proteins: mean over proteins) 0.421
SaProt (650M)foundation model0.457mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.458Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.313Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.275Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.268
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.336Spearman (Activity assays: mean over proteins) 0.458Spearman (Binding assays: mean over proteins) 0.378Spearman (Expression assays: mean over proteins) 0.488Spearman (Organismal fitness assays: mean over proteins) 0.366Spearman (Stability assays: mean over proteins) 0.592Spearman (High MSA depth proteins: mean over proteins) 0.546Spearman (Low MSA depth proteins: mean over proteins) 0.394Spearman (Medium MSA depth proteins: mean over proteins) 0.446Spearman (Human proteins: mean over proteins) 0.478Spearman (Other eukaryote proteins: mean over proteins) 0.529Spearman (Prokaryote proteins: mean over proteins) 0.514Spearman (Virus proteins: mean over proteins) 0.32
S2Ffoundation model0.456mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.47Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.281Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.289Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.251
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.297Spearman (Activity assays: mean over proteins) 0.459Spearman (Binding assays: mean over proteins) 0.391Spearman (Expression assays: mean over proteins) 0.456Spearman (Organismal fitness assays: mean over proteins) 0.404Spearman (Stability assays: mean over proteins) 0.568Spearman (High MSA depth proteins: mean over proteins) 0.531Spearman (Low MSA depth proteins: mean over proteins) 0.404Spearman (Medium MSA depth proteins: mean over proteins) 0.457Spearman (Human proteins: mean over proteins) 0.473Spearman (Other eukaryote proteins: mean over proteins) 0.514Spearman (Prokaryote proteins: mean over proteins) 0.496Spearman (Virus proteins: mean over proteins) 0.396
TranceptEVE L0.456mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.446Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.278Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.349Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.331
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.382Spearman (Activity assays: mean over proteins) 0.487Spearman (Binding assays: mean over proteins) 0.376Spearman (Expression assays: mean over proteins) 0.457Spearman (Organismal fitness assays: mean over proteins) 0.459Spearman (Stability assays: mean over proteins) 0.5Spearman (High MSA depth proteins: mean over proteins) 0.49Spearman (Low MSA depth proteins: mean over proteins) 0.436Spearman (Medium MSA depth proteins: mean over proteins) 0.472Spearman (Human proteins: mean over proteins) 0.473Spearman (Other eukaryote proteins: mean over proteins) 0.513Spearman (Prokaryote proteins: mean over proteins) 0.455Spearman (Virus proteins: mean over proteins) 0.461
GEMME0.455mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.448Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.276Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.33Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.341
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.414Spearman (Activity assays: mean over proteins) 0.482Spearman (Binding assays: mean over proteins) 0.383Spearman (Expression assays: mean over proteins) 0.438Spearman (Organismal fitness assays: mean over proteins) 0.452Spearman (Stability assays: mean over proteins) 0.519Spearman (High MSA depth proteins: mean over proteins) 0.493Spearman (Low MSA depth proteins: mean over proteins) 0.446Spearman (Medium MSA depth proteins: mean over proteins) 0.474Spearman (Human proteins: mean over proteins) 0.469Spearman (Other eukaryote proteins: mean over proteins) 0.516Spearman (Prokaryote proteins: mean over proteins) 0.467Spearman (Virus proteins: mean over proteins) 0.472
TranceptEVE M0.455mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.442Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.282Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.312Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.318
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.375Spearman (Activity assays: mean over proteins) 0.479Spearman (Binding assays: mean over proteins) 0.386Spearman (Expression assays: mean over proteins) 0.452Spearman (Organismal fitness assays: mean over proteins) 0.454Spearman (Stability assays: mean over proteins) 0.502Spearman (High MSA depth proteins: mean over proteins) 0.487Spearman (Low MSA depth proteins: mean over proteins) 0.424Spearman (Medium MSA depth proteins: mean over proteins) 0.472Spearman (Human proteins: mean over proteins) 0.474Spearman (Other eukaryote proteins: mean over proteins) 0.513Spearman (Prokaryote proteins: mean over proteins) 0.45Spearman (Virus proteins: mean over proteins) 0.446
TranceptEVE S0.452mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.437Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.276Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.311Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.315
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.372Spearman (Activity assays: mean over proteins) 0.475Spearman (Binding assays: mean over proteins) 0.396Spearman (Expression assays: mean over proteins) 0.443Spearman (Organismal fitness assays: mean over proteins) 0.449Spearman (Stability assays: mean over proteins) 0.497Spearman (High MSA depth proteins: mean over proteins) 0.482Spearman (Low MSA depth proteins: mean over proteins) 0.434Spearman (Medium MSA depth proteins: mean over proteins) 0.465Spearman (Human proteins: mean over proteins) 0.47Spearman (Other eukaryote proteins: mean over proteins) 0.504Spearman (Prokaryote proteins: mean over proteins) 0.453Spearman (Virus proteins: mean over proteins) 0.438
ProtSSN (ensemble)foundation model0.449mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.459Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.291Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.292Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.244
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.298Spearman (Activity assays: mean over proteins) 0.466Spearman (Binding assays: mean over proteins) 0.366Spearman (Expression assays: mean over proteins) 0.449Spearman (Organismal fitness assays: mean over proteins) 0.396Spearman (Stability assays: mean over proteins) 0.568Spearman (High MSA depth proteins: mean over proteins) 0.524Spearman (Low MSA depth proteins: mean over proteins) 0.409Spearman (Medium MSA depth proteins: mean over proteins) 0.454Spearman (Human proteins: mean over proteins) 0.47Spearman (Other eukaryote proteins: mean over proteins) 0.528Spearman (Prokaryote proteins: mean over proteins) 0.492Spearman (Virus proteins: mean over proteins) 0.37
ProtSSN (k=20, h=1280)foundation model0.442mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.45Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.279Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.288Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.24
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.297Spearman (Activity assays: mean over proteins) 0.458Spearman (Binding assays: mean over proteins) 0.366Spearman (Expression assays: mean over proteins) 0.435Spearman (Organismal fitness assays: mean over proteins) 0.385Spearman (Stability assays: mean over proteins) 0.566Spearman (High MSA depth proteins: mean over proteins) 0.52Spearman (Low MSA depth proteins: mean over proteins) 0.402Spearman (Medium MSA depth proteins: mean over proteins) 0.445Spearman (Human proteins: mean over proteins) 0.464Spearman (Other eukaryote proteins: mean over proteins) 0.525Spearman (Prokaryote proteins: mean over proteins) 0.483Spearman (Virus proteins: mean over proteins) 0.363
ProtSSN (k=20, h=512)foundation model0.440mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.45Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.29Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.306Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.262
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.31Spearman (Activity assays: mean over proteins) 0.457Spearman (Binding assays: mean over proteins) 0.353Spearman (Expression assays: mean over proteins) 0.437Spearman (Organismal fitness assays: mean over proteins) 0.391Spearman (Stability assays: mean over proteins) 0.563Spearman (High MSA depth proteins: mean over proteins) 0.515Spearman (Low MSA depth proteins: mean over proteins) 0.4Spearman (Medium MSA depth proteins: mean over proteins) 0.45Spearman (Human proteins: mean over proteins) 0.458Spearman (Other eukaryote proteins: mean over proteins) 0.524Spearman (Prokaryote proteins: mean over proteins) 0.488Spearman (Virus proteins: mean over proteins) 0.373
EVE (ensemble)0.439mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.428Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.273Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.31Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.31
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.355Spearman (Activity assays: mean over proteins) 0.464Spearman (Binding assays: mean over proteins) 0.386Spearman (Expression assays: mean over proteins) 0.408Spearman (Organismal fitness assays: mean over proteins) 0.447Spearman (Stability assays: mean over proteins) 0.491Spearman (High MSA depth proteins: mean over proteins) 0.477Spearman (Low MSA depth proteins: mean over proteins) 0.42Spearman (Medium MSA depth proteins: mean over proteins) 0.457Spearman (Human proteins: mean over proteins) 0.454Spearman (Other eukaryote proteins: mean over proteins) 0.495Spearman (Prokaryote proteins: mean over proteins) 0.457Spearman (Virus proteins: mean over proteins) 0.434
ProtSSN (k=20, h=768)foundation model0.439mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.448Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.294Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.282Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.242
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.31Spearman (Activity assays: mean over proteins) 0.459Spearman (Binding assays: mean over proteins) 0.347Spearman (Expression assays: mean over proteins) 0.439Spearman (Organismal fitness assays: mean over proteins) 0.387Spearman (Stability assays: mean over proteins) 0.563Spearman (High MSA depth proteins: mean over proteins) 0.52Spearman (Low MSA depth proteins: mean over proteins) 0.394Spearman (Medium MSA depth proteins: mean over proteins) 0.446Spearman (Human proteins: mean over proteins) 0.462Spearman (Other eukaryote proteins: mean over proteins) 0.525Spearman (Prokaryote proteins: mean over proteins) 0.485Spearman (Virus proteins: mean over proteins) 0.357
ProSST (K=20)foundation model0.438mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.44Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.375Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.311Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.278
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.348Spearman (Activity assays: mean over proteins) 0.392Spearman (Binding assays: mean over proteins) 0.41Spearman (Expression assays: mean over proteins) 0.447Spearman (Organismal fitness assays: mean over proteins) 0.354Spearman (Stability assays: mean over proteins) 0.589Spearman (High MSA depth proteins: mean over proteins) 0.525Spearman (Low MSA depth proteins: mean over proteins) 0.408Spearman (Medium MSA depth proteins: mean over proteins) 0.42Spearman (Human proteins: mean over proteins) 0.443Spearman (Other eukaryote proteins: mean over proteins) 0.506Spearman (Prokaryote proteins: mean over proteins) 0.477Spearman (Virus proteins: mean over proteins) 0.387
ProtSSN (k=30, h=512)foundation model0.438mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.445Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.275Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.278Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.238
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.291Spearman (Activity assays: mean over proteins) 0.455Spearman (Binding assays: mean over proteins) 0.35Spearman (Expression assays: mean over proteins) 0.443Spearman (Organismal fitness assays: mean over proteins) 0.384Spearman (Stability assays: mean over proteins) 0.557Spearman (High MSA depth proteins: mean over proteins) 0.511Spearman (Low MSA depth proteins: mean over proteins) 0.4Spearman (Medium MSA depth proteins: mean over proteins) 0.444Spearman (Human proteins: mean over proteins) 0.461Spearman (Other eukaryote proteins: mean over proteins) 0.519Spearman (Prokaryote proteins: mean over proteins) 0.479Spearman (Virus proteins: mean over proteins) 0.356
ProtSSN (k=30, h=768)foundation model0.438mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.446Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.284Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.281Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.236
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.297Spearman (Activity assays: mean over proteins) 0.457Spearman (Binding assays: mean over proteins) 0.351Spearman (Expression assays: mean over proteins) 0.435Spearman (Organismal fitness assays: mean over proteins) 0.384Spearman (Stability assays: mean over proteins) 0.561Spearman (High MSA depth proteins: mean over proteins) 0.515Spearman (Low MSA depth proteins: mean over proteins) 0.393Spearman (Medium MSA depth proteins: mean over proteins) 0.446Spearman (Human proteins: mean over proteins) 0.458Spearman (Other eukaryote proteins: mean over proteins) 0.525Spearman (Prokaryote proteins: mean over proteins) 0.484Spearman (Virus proteins: mean over proteins) 0.356
ProtSSN (k=30, h=1280)foundation model0.437mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.444Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.299Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.282Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.23
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.3Spearman (Activity assays: mean over proteins) 0.454Spearman (Binding assays: mean over proteins) 0.357Spearman (Expression assays: mean over proteins) 0.431Spearman (Organismal fitness assays: mean over proteins) 0.384Spearman (Stability assays: mean over proteins) 0.561Spearman (High MSA depth proteins: mean over proteins) 0.52Spearman (Low MSA depth proteins: mean over proteins) 0.395Spearman (Medium MSA depth proteins: mean over proteins) 0.44Spearman (Human proteins: mean over proteins) 0.46Spearman (Other eukaryote proteins: mean over proteins) 0.522Spearman (Prokaryote proteins: mean over proteins) 0.483Spearman (Virus proteins: mean over proteins) 0.35
VESPAmachine learning0.435mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.435Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.181Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.348Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.308
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.328Spearman (Activity assays: mean over proteins) 0.468Spearman (Binding assays: mean over proteins) 0.366Spearman (Expression assays: mean over proteins) 0.404Spearman (Organismal fitness assays: mean over proteins) 0.439Spearman (Stability assays: mean over proteins) 0.5Spearman (High MSA depth proteins: mean over proteins) 0.484Spearman (Low MSA depth proteins: mean over proteins) 0.42Spearman (Medium MSA depth proteins: mean over proteins) 0.455Spearman (Human proteins: mean over proteins) 0.44Spearman (Other eukaryote proteins: mean over proteins) 0.503Spearman (Prokaryote proteins: mean over proteins) 0.474Spearman (Virus proteins: mean over proteins) 0.443
Tranception Lfoundation model0.434mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.422Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.254Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.346Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.325
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.387Spearman (Activity assays: mean over proteins) 0.465Spearman (Binding assays: mean over proteins) 0.349Spearman (Expression assays: mean over proteins) 0.45Spearman (Organismal fitness assays: mean over proteins) 0.435Spearman (Stability assays: mean over proteins) 0.471Spearman (High MSA depth proteins: mean over proteins) 0.471Spearman (Low MSA depth proteins: mean over proteins) 0.421Spearman (Medium MSA depth proteins: mean over proteins) 0.443Spearman (Human proteins: mean over proteins) 0.455Spearman (Other eukaryote proteins: mean over proteins) 0.497Spearman (Prokaryote proteins: mean over proteins) 0.414Spearman (Virus proteins: mean over proteins) 0.438
ProtSSN (k=10, h=1280)foundation model0.433mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.441Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.245Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.257Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.217
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.282Spearman (Activity assays: mean over proteins) 0.446Spearman (Binding assays: mean over proteins) 0.352Spearman (Expression assays: mean over proteins) 0.436Spearman (Organismal fitness assays: mean over proteins) 0.381Spearman (Stability assays: mean over proteins) 0.548Spearman (High MSA depth proteins: mean over proteins) 0.503Spearman (Low MSA depth proteins: mean over proteins) 0.4Spearman (Medium MSA depth proteins: mean over proteins) 0.437Spearman (Human proteins: mean over proteins) 0.455Spearman (Other eukaryote proteins: mean over proteins) 0.512Spearman (Prokaryote proteins: mean over proteins) 0.47Spearman (Virus proteins: mean over proteins) 0.358
EVE (single)0.432mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.422Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.271Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.305Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.308
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.359Spearman (Activity assays: mean over proteins) 0.458Spearman (Binding assays: mean over proteins) 0.372Spearman (Expression assays: mean over proteins) 0.404Spearman (Organismal fitness assays: mean over proteins) 0.441Spearman (Stability assays: mean over proteins) 0.487Spearman (High MSA depth proteins: mean over proteins) 0.473Spearman (Low MSA depth proteins: mean over proteins) 0.411Spearman (Medium MSA depth proteins: mean over proteins) 0.452Spearman (Human proteins: mean over proteins) 0.446Spearman (Other eukaryote proteins: mean over proteins) 0.491Spearman (Prokaryote proteins: mean over proteins) 0.454Spearman (Virus proteins: mean over proteins) 0.43
MSA Transformer (ensemble)foundation model0.432mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.427Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.221Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.365Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.369
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.397Spearman (Activity assays: mean over proteins) 0.473Spearman (Binding assays: mean over proteins) 0.329Spearman (Expression assays: mean over proteins) 0.446Spearman (Organismal fitness assays: mean over proteins) 0.419Spearman (Stability assays: mean over proteins) 0.492Spearman (High MSA depth proteins: mean over proteins) 0.479Spearman (Low MSA depth proteins: mean over proteins) 0.375Spearman (Medium MSA depth proteins: mean over proteins) 0.456Spearman (Human proteins: mean over proteins) 0.439Spearman (Other eukaryote proteins: mean over proteins) 0.516Spearman (Prokaryote proteins: mean over proteins) 0.446Spearman (Virus proteins: mean over proteins) 0.421
ProtSSN (k=10, h=512)foundation model0.430mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.437Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.281Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.266Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.217
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.287Spearman (Activity assays: mean over proteins) 0.451Spearman (Binding assays: mean over proteins) 0.344Spearman (Expression assays: mean over proteins) 0.42Spearman (Organismal fitness assays: mean over proteins) 0.376Spearman (Stability assays: mean over proteins) 0.557Spearman (High MSA depth proteins: mean over proteins) 0.51Spearman (Low MSA depth proteins: mean over proteins) 0.398Spearman (Medium MSA depth proteins: mean over proteins) 0.434Spearman (Human proteins: mean over proteins) 0.454Spearman (Other eukaryote proteins: mean over proteins) 0.521Spearman (Prokaryote proteins: mean over proteins) 0.478Spearman (Virus proteins: mean over proteins) 0.338
Tranception Mfoundation model0.428mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.412Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.251Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.255Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.273
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.353Spearman (Activity assays: mean over proteins) 0.448Spearman (Binding assays: mean over proteins) 0.361Spearman (Expression assays: mean over proteins) 0.441Spearman (Organismal fitness assays: mean over proteins) 0.424Spearman (Stability assays: mean over proteins) 0.465Spearman (High MSA depth proteins: mean over proteins) 0.456Spearman (Low MSA depth proteins: mean over proteins) 0.406Spearman (Medium MSA depth proteins: mean over proteins) 0.437Spearman (Human proteins: mean over proteins) 0.452Spearman (Other eukaryote proteins: mean over proteins) 0.489Spearman (Prokaryote proteins: mean over proteins) 0.397Spearman (Virus proteins: mean over proteins) 0.414
SiteRM0.424mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.401Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.223Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.313Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.309
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.363Spearman (Activity assays: mean over proteins) 0.453Spearman (Binding assays: mean over proteins) 0.388Spearman (Expression assays: mean over proteins) 0.39Spearman (Organismal fitness assays: mean over proteins) 0.437Spearman (Stability assays: mean over proteins) 0.449Spearman (High MSA depth proteins: mean over proteins) 0.429Spearman (Low MSA depth proteins: mean over proteins) 0.446Spearman (Medium MSA depth proteins: mean over proteins) 0.438Spearman (Human proteins: mean over proteins) 0.437Spearman (Other eukaryote proteins: mean over proteins) 0.471Spearman (Prokaryote proteins: mean over proteins) 0.399Spearman (Virus proteins: mean over proteins) 0.462
ESM-IF1foundation model0.422mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.44Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.35Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.301Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.294
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.358Spearman (Activity assays: mean over proteins) 0.368Spearman (Binding assays: mean over proteins) 0.389Spearman (Expression assays: mean over proteins) 0.407Spearman (Organismal fitness assays: mean over proteins) 0.324Spearman (Stability assays: mean over proteins) 0.624Spearman (High MSA depth proteins: mean over proteins) 0.549Spearman (Low MSA depth proteins: mean over proteins) 0.292Spearman (Medium MSA depth proteins: mean over proteins) 0.427Spearman (Human proteins: mean over proteins) 0.417Spearman (Other eukaryote proteins: mean over proteins) 0.502Spearman (Prokaryote proteins: mean over proteins) 0.498Spearman (Virus proteins: mean over proteins) 0.389
ProtSSN (k=10, h=768)foundation model0.422mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.43Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.269Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.27Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.215
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.278Spearman (Activity assays: mean over proteins) 0.441Spearman (Binding assays: mean over proteins) 0.337Spearman (Expression assays: mean over proteins) 0.417Spearman (Organismal fitness assays: mean over proteins) 0.37Spearman (Stability assays: mean over proteins) 0.547Spearman (High MSA depth proteins: mean over proteins) 0.497Spearman (Low MSA depth proteins: mean over proteins) 0.382Spearman (Medium MSA depth proteins: mean over proteins) 0.431Spearman (Human proteins: mean over proteins) 0.446Spearman (Other eukaryote proteins: mean over proteins) 0.503Spearman (Prokaryote proteins: mean over proteins) 0.467Spearman (Virus proteins: mean over proteins) 0.346
DeepSequence (ensemble)0.419mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.405Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.263Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.314Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.322
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.378Spearman (Activity assays: mean over proteins) 0.455Spearman (Binding assays: mean over proteins) 0.363Spearman (Expression assays: mean over proteins) 0.39Spearman (Organismal fitness assays: mean over proteins) 0.411Spearman (Stability assays: mean over proteins) 0.476Spearman (High MSA depth proteins: mean over proteins) 0.474Spearman (Low MSA depth proteins: mean over proteins) 0.37Spearman (Medium MSA depth proteins: mean over proteins) 0.431Spearman (Human proteins: mean over proteins) 0.443Spearman (Other eukaryote proteins: mean over proteins) 0.486Spearman (Prokaryote proteins: mean over proteins) 0.439Spearman (Virus proteins: mean over proteins) 0.358
Tranception Sfoundation model0.418mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.398Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.244Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.264Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.279
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.352Spearman (Activity assays: mean over proteins) 0.436Spearman (Binding assays: mean over proteins) 0.372Spearman (Expression assays: mean over proteins) 0.42Spearman (Organismal fitness assays: mean over proteins) 0.412Spearman (Stability assays: mean over proteins) 0.452Spearman (High MSA depth proteins: mean over proteins) 0.442Spearman (Low MSA depth proteins: mean over proteins) 0.418Spearman (Medium MSA depth proteins: mean over proteins) 0.421Spearman (Human proteins: mean over proteins) 0.44Spearman (Other eukaryote proteins: mean over proteins) 0.476Spearman (Prokaryote proteins: mean over proteins) 0.391Spearman (Virus proteins: mean over proteins) 0.401
MSA Transformer (single)foundation model0.417mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.412Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.208Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.363Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.361
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.39Spearman (Activity assays: mean over proteins) 0.455Spearman (Binding assays: mean over proteins) 0.312Spearman (Expression assays: mean over proteins) 0.429Spearman (Organismal fitness assays: mean over proteins) 0.412Spearman (Stability assays: mean over proteins) 0.475Spearman (High MSA depth proteins: mean over proteins) 0.465Spearman (Low MSA depth proteins: mean over proteins) 0.364Spearman (Medium MSA depth proteins: mean over proteins) 0.441Spearman (Human proteins: mean over proteins) 0.43Spearman (Other eukaryote proteins: mean over proteins) 0.501Spearman (Prokaryote proteins: mean over proteins) 0.426Spearman (Virus proteins: mean over proteins) 0.406
ESM2 (650M)foundation model0.414mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.422Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.248Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.205Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.163
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.218Spearman (Activity assays: mean over proteins) 0.425Spearman (Binding assays: mean over proteins) 0.337Spearman (Expression assays: mean over proteins) 0.415Spearman (Organismal fitness assays: mean over proteins) 0.368Spearman (Stability assays: mean over proteins) 0.523Spearman (High MSA depth proteins: mean over proteins) 0.513Spearman (Low MSA depth proteins: mean over proteins) 0.338Spearman (Medium MSA depth proteins: mean over proteins) 0.409Spearman (Human proteins: mean over proteins) 0.457Spearman (Other eukaryote proteins: mean over proteins) 0.486Spearman (Prokaryote proteins: mean over proteins) 0.458Spearman (Virus proteins: mean over proteins) 0.261
DeepSequence (single)0.407mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.392Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.253Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.285Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.306
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.37Spearman (Activity assays: mean over proteins) 0.447Spearman (Binding assays: mean over proteins) 0.349Spearman (Expression assays: mean over proteins) 0.371Spearman (Organismal fitness assays: mean over proteins) 0.396Spearman (Stability assays: mean over proteins) 0.473Spearman (High MSA depth proteins: mean over proteins) 0.464Spearman (Low MSA depth proteins: mean over proteins) 0.372Spearman (Medium MSA depth proteins: mean over proteins) 0.419Spearman (Human proteins: mean over proteins) 0.437Spearman (Other eukaryote proteins: mean over proteins) 0.479Spearman (Prokaryote proteins: mean over proteins) 0.43Spearman (Virus proteins: mean over proteins) 0.338
ESM-1v (ensemble)foundation model0.407mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.403Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.215Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.173Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.153
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.218Spearman (Activity assays: mean over proteins) 0.42Spearman (Binding assays: mean over proteins) 0.32Spearman (Expression assays: mean over proteins) 0.429Spearman (Organismal fitness assays: mean over proteins) 0.386Spearman (Stability assays: mean over proteins) 0.477Spearman (High MSA depth proteins: mean over proteins) 0.495Spearman (Low MSA depth proteins: mean over proteins) 0.316Spearman (Medium MSA depth proteins: mean over proteins) 0.409Spearman (Human proteins: mean over proteins) 0.458Spearman (Other eukaryote proteins: mean over proteins) 0.464Spearman (Prokaryote proteins: mean over proteins) 0.413Spearman (Virus proteins: mean over proteins) 0.294
SaProt (35M)foundation model0.407mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.41Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.356Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.187Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.187
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.245Spearman (Activity assays: mean over proteins) 0.372Spearman (Binding assays: mean over proteins) 0.357Spearman (Expression assays: mean over proteins) 0.439Spearman (Organismal fitness assays: mean over proteins) 0.289Spearman (Stability assays: mean over proteins) 0.575Spearman (High MSA depth proteins: mean over proteins) 0.514Spearman (Low MSA depth proteins: mean over proteins) 0.325Spearman (Medium MSA depth proteins: mean over proteins) 0.385Spearman (Human proteins: mean over proteins) 0.443Spearman (Other eukaryote proteins: mean over proteins) 0.492Spearman (Prokaryote proteins: mean over proteins) 0.432Spearman (Virus proteins: mean over proteins) 0.242
ESM-C (300M)foundation model0.406mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.415Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.258Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.191Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.155
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.217Spearman (Activity assays: mean over proteins) 0.423Spearman (Binding assays: mean over proteins) 0.315Spearman (Expression assays: mean over proteins) 0.408Spearman (Organismal fitness assays: mean over proteins) 0.36Spearman (Stability assays: mean over proteins) 0.526Spearman (High MSA depth proteins: mean over proteins) 0.52Spearman (Low MSA depth proteins: mean over proteins) 0.337Spearman (Medium MSA depth proteins: mean over proteins) 0.399Spearman (Human proteins: mean over proteins) 0.468Spearman (Other eukaryote proteins: mean over proteins) 0.481Spearman (Prokaryote proteins: mean over proteins) 0.441Spearman (Virus proteins: mean over proteins) 0.242
ESM2 (3B)foundation model0.406mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.414Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.215Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.194Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.166
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.217Spearman (Activity assays: mean over proteins) 0.417Spearman (Binding assays: mean over proteins) 0.321Spearman (Expression assays: mean over proteins) 0.403Spearman (Organismal fitness assays: mean over proteins) 0.378Spearman (Stability assays: mean over proteins) 0.509Spearman (High MSA depth proteins: mean over proteins) 0.485Spearman (Low MSA depth proteins: mean over proteins) 0.336Spearman (Medium MSA depth proteins: mean over proteins) 0.423Spearman (Human proteins: mean over proteins) 0.442Spearman (Other eukaryote proteins: mean over proteins) 0.477Spearman (Prokaryote proteins: mean over proteins) 0.458Spearman (Virus proteins: mean over proteins) 0.294
ESM-C (600M)foundation model0.405mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.416Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.246Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.197Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.15
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.202Spearman (Activity assays: mean over proteins) 0.423Spearman (Binding assays: mean over proteins) 0.294Spearman (Expression assays: mean over proteins) 0.42Spearman (Organismal fitness assays: mean over proteins) 0.362Spearman (Stability assays: mean over proteins) 0.528Spearman (High MSA depth proteins: mean over proteins) 0.515Spearman (Low MSA depth proteins: mean over proteins) 0.331Spearman (Medium MSA depth proteins: mean over proteins) 0.407Spearman (Human proteins: mean over proteins) 0.462Spearman (Other eukaryote proteins: mean over proteins) 0.481Spearman (Prokaryote proteins: mean over proteins) 0.459Spearman (Virus proteins: mean over proteins) 0.241
ESM2 (15B)foundation model0.400mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.405Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.202Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.219Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.173
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.234Spearman (Activity assays: mean over proteins) 0.405Spearman (Binding assays: mean over proteins) 0.317Spearman (Expression assays: mean over proteins) 0.405Spearman (Organismal fitness assays: mean over proteins) 0.387Spearman (Stability assays: mean over proteins) 0.488Spearman (High MSA depth proteins: mean over proteins) 0.467Spearman (Low MSA depth proteins: mean over proteins) 0.341Spearman (Medium MSA depth proteins: mean over proteins) 0.422Spearman (Human proteins: mean over proteins) 0.432Spearman (Other eukaryote proteins: mean over proteins) 0.467Spearman (Prokaryote proteins: mean over proteins) 0.436Spearman (Virus proteins: mean over proteins) 0.333
MIF-STfoundation model0.400mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.431Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.263Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.327Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.298
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.298Spearman (Activity assays: mean over proteins) 0.39Spearman (Binding assays: mean over proteins) 0.321Spearman (Expression assays: mean over proteins) 0.438Spearman (Organismal fitness assays: mean over proteins) 0.366Spearman (Stability assays: mean over proteins) 0.485Spearman (High MSA depth proteins: mean over proteins) 0.453Spearman (Low MSA depth proteins: mean over proteins) 0.371Spearman (Medium MSA depth proteins: mean over proteins) 0.404Spearman (Human proteins: mean over proteins) 0.399Spearman (Other eukaryote proteins: mean over proteins) 0.413Spearman (Prokaryote proteins: mean over proteins) 0.457Spearman (Virus proteins: mean over proteins) 0.405
xTrimoPGLM-3B-MLMfoundation model0.399mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.399Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.217Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.183Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.136
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.189Spearman (Activity assays: mean over proteins) 0.408Spearman (Binding assays: mean over proteins) 0.308Spearman (Expression assays: mean over proteins) 0.396Spearman (Organismal fitness assays: mean over proteins) 0.4Spearman (Stability assays: mean over proteins) 0.482Spearman (High MSA depth proteins: mean over proteins) 0.474Spearman (Low MSA depth proteins: mean over proteins) 0.332Spearman (Medium MSA depth proteins: mean over proteins) 0.423Spearman (Human proteins: mean over proteins) 0.426Spearman (Other eukaryote proteins: mean over proteins) 0.449Spearman (Prokaryote proteins: mean over proteins) 0.442Spearman (Virus proteins: mean over proteins) 0.375
xTrimoPGLM-10B-MLMfoundation model0.396mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.395Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.202Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.176Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.137
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.19Spearman (Activity assays: mean over proteins) 0.405Spearman (Binding assays: mean over proteins) 0.301Spearman (Expression assays: mean over proteins) 0.398Spearman (Organismal fitness assays: mean over proteins) 0.394Spearman (Stability assays: mean over proteins) 0.481Spearman (High MSA depth proteins: mean over proteins) 0.48Spearman (Low MSA depth proteins: mean over proteins) 0.327Spearman (Medium MSA depth proteins: mean over proteins) 0.414Spearman (Human proteins: mean over proteins) 0.421Spearman (Other eukaryote proteins: mean over proteins) 0.445Spearman (Prokaryote proteins: mean over proteins) 0.444Spearman (Virus proteins: mean over proteins) 0.368
EVmutation0.395mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.376Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.273Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.327Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.318
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.394Spearman (Activity assays: mean over proteins) 0.44Spearman (Binding assays: mean over proteins) 0.317Spearman (Expression assays: mean over proteins) 0.378Spearman (Organismal fitness assays: mean over proteins) 0.41Spearman (Stability assays: mean over proteins) 0.43Spearman (High MSA depth proteins: mean over proteins) 0.404Spearman (Low MSA depth proteins: mean over proteins) 0.399Spearman (Medium MSA depth proteins: mean over proteins) 0.426Spearman (Human proteins: mean over proteins) 0.41Spearman (Other eukaryote proteins: mean over proteins) 0.448Spearman (Prokaryote proteins: mean over proteins) 0.414Spearman (Virus proteins: mean over proteins) 0.393
ESM-1bfoundation model0.394mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.383Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.226Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.172Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.15
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.27Spearman (Activity assays: mean over proteins) 0.428Spearman (Binding assays: mean over proteins) 0.287Spearman (Expression assays: mean over proteins) 0.406Spearman (Organismal fitness assays: mean over proteins) 0.349Spearman (Stability assays: mean over proteins) 0.5Spearman (High MSA depth proteins: mean over proteins) 0.48Spearman (Low MSA depth proteins: mean over proteins) 0.365Spearman (Medium MSA depth proteins: mean over proteins) 0.396Spearman (Human proteins: mean over proteins) 0.435Spearman (Other eukaryote proteins: mean over proteins) 0.491Spearman (Prokaryote proteins: mean over proteins) 0.438Spearman (Virus proteins: mean over proteins) 0.26
VESPAlmachine learning0.393mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.386Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.141Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.321Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.282
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.32Spearman (Activity assays: mean over proteins) 0.429Spearman (Binding assays: mean over proteins) 0.347Spearman (Expression assays: mean over proteins) 0.326Spearman (Organismal fitness assays: mean over proteins) 0.403Spearman (Stability assays: mean over proteins) 0.461Spearman (High MSA depth proteins: mean over proteins) 0.449Spearman (Low MSA depth proteins: mean over proteins) 0.377Spearman (Medium MSA depth proteins: mean over proteins) 0.411Spearman (Human proteins: mean over proteins) 0.394Spearman (Other eukaryote proteins: mean over proteins) 0.472Spearman (Prokaryote proteins: mean over proteins) 0.434Spearman (Virus proteins: mean over proteins) 0.403
Progen3 3Bfoundation model0.392mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.388Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.179Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.226Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.204
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.256Spearman (Activity assays: mean over proteins) 0.41Spearman (Binding assays: mean over proteins) 0.287Spearman (Expression assays: mean over proteins) 0.428Spearman (Organismal fitness assays: mean over proteins) 0.4Spearman (Stability assays: mean over proteins) 0.438Spearman (High MSA depth proteins: mean over proteins) 0.453Spearman (Low MSA depth proteins: mean over proteins) 0.325Spearman (Medium MSA depth proteins: mean over proteins) 0.407Spearman (Human proteins: mean over proteins) 0.41Spearman (Other eukaryote proteins: mean over proteins) 0.433Spearman (Prokaryote proteins: mean over proteins) 0.392Spearman (Virus proteins: mean over proteins) 0.414
Progen2 XLfoundation model0.391mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.384Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.182Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.271Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.234
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.28Spearman (Activity assays: mean over proteins) 0.402Spearman (Binding assays: mean over proteins) 0.302Spearman (Expression assays: mean over proteins) 0.418Spearman (Organismal fitness assays: mean over proteins) 0.387Spearman (Stability assays: mean over proteins) 0.445Spearman (High MSA depth proteins: mean over proteins) 0.442Spearman (Low MSA depth proteins: mean over proteins) 0.323Spearman (Medium MSA depth proteins: mean over proteins) 0.412Spearman (Human proteins: mean over proteins) 0.386Spearman (Other eukaryote proteins: mean over proteins) 0.458Spearman (Prokaryote proteins: mean over proteins) 0.418Spearman (Virus proteins: mean over proteins) 0.402
Progen3 1Bfoundation model0.389mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.382Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.164Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.217Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.192
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.243Spearman (Activity assays: mean over proteins) 0.409Spearman (Binding assays: mean over proteins) 0.303Spearman (Expression assays: mean over proteins) 0.428Spearman (Organismal fitness assays: mean over proteins) 0.396Spearman (Stability assays: mean over proteins) 0.408Spearman (High MSA depth proteins: mean over proteins) 0.438Spearman (Low MSA depth proteins: mean over proteins) 0.321Spearman (Medium MSA depth proteins: mean over proteins) 0.396Spearman (Human proteins: mean over proteins) 0.408Spearman (Other eukaryote proteins: mean over proteins) 0.418Spearman (Prokaryote proteins: mean over proteins) 0.368Spearman (Virus proteins: mean over proteins) 0.401
ESM2 (150M)foundation model0.387mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.387Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.246Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.146Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.16
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.231Spearman (Activity assays: mean over proteins) 0.391Spearman (Binding assays: mean over proteins) 0.326Spearman (Expression assays: mean over proteins) 0.402Spearman (Organismal fitness assays: mean over proteins) 0.305Spearman (Stability assays: mean over proteins) 0.51Spearman (High MSA depth proteins: mean over proteins) 0.494Spearman (Low MSA depth proteins: mean over proteins) 0.319Spearman (Medium MSA depth proteins: mean over proteins) 0.359Spearman (Human proteins: mean over proteins) 0.45Spearman (Other eukaryote proteins: mean over proteins) 0.475Spearman (Prokaryote proteins: mean over proteins) 0.398Spearman (Virus proteins: mean over proteins) 0.157
MIFfoundation model0.383mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.412Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.272Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.272Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.245
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.24Spearman (Activity assays: mean over proteins) 0.327Spearman (Binding assays: mean over proteins) 0.336Spearman (Expression assays: mean over proteins) 0.43Spearman (Organismal fitness assays: mean over proteins) 0.3Spearman (Stability assays: mean over proteins) 0.522Spearman (High MSA depth proteins: mean over proteins) 0.448Spearman (Low MSA depth proteins: mean over proteins) 0.344Spearman (Medium MSA depth proteins: mean over proteins) 0.374Spearman (Human proteins: mean over proteins) 0.398Spearman (Other eukaryote proteins: mean over proteins) 0.387Spearman (Prokaryote proteins: mean over proteins) 0.417Spearman (Virus proteins: mean over proteins) 0.365
Progen2 Lfoundation model0.380mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.371Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.142Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.225Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.207
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.258Spearman (Activity assays: mean over proteins) 0.406Spearman (Binding assays: mean over proteins) 0.293Spearman (Expression assays: mean over proteins) 0.427Spearman (Organismal fitness assays: mean over proteins) 0.379Spearman (Stability assays: mean over proteins) 0.396Spearman (High MSA depth proteins: mean over proteins) 0.414Spearman (Low MSA depth proteins: mean over proteins) 0.339Spearman (Medium MSA depth proteins: mean over proteins) 0.39Spearman (Human proteins: mean over proteins) 0.411Spearman (Other eukaryote proteins: mean over proteins) 0.432Spearman (Prokaryote proteins: mean over proteins) 0.364Spearman (Virus proteins: mean over proteins) 0.323
Progen2 Mfoundation model0.380mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.373Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.131Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.152Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.137
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.177Spearman (Activity assays: mean over proteins) 0.393Spearman (Binding assays: mean over proteins) 0.295Spearman (Expression assays: mean over proteins) 0.433Spearman (Organismal fitness assays: mean over proteins) 0.383Spearman (Stability assays: mean over proteins) 0.396Spearman (High MSA depth proteins: mean over proteins) 0.422Spearman (Low MSA depth proteins: mean over proteins) 0.307Spearman (Medium MSA depth proteins: mean over proteins) 0.391Spearman (Human proteins: mean over proteins) 0.413Spearman (Other eukaryote proteins: mean over proteins) 0.417Spearman (Prokaryote proteins: mean over proteins) 0.356Spearman (Virus proteins: mean over proteins) 0.335
xTrimoPGLM-1B-MLMfoundation model0.379mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.374Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.187Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.189Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.168
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.227Spearman (Activity assays: mean over proteins) 0.39Spearman (Binding assays: mean over proteins) 0.298Spearman (Expression assays: mean over proteins) 0.406Spearman (Organismal fitness assays: mean over proteins) 0.357Spearman (Stability assays: mean over proteins) 0.445Spearman (High MSA depth proteins: mean over proteins) 0.463Spearman (Low MSA depth proteins: mean over proteins) 0.324Spearman (Medium MSA depth proteins: mean over proteins) 0.372Spearman (Human proteins: mean over proteins) 0.426Spearman (Other eukaryote proteins: mean over proteins) 0.441Spearman (Prokaryote proteins: mean over proteins) 0.402Spearman (Virus proteins: mean over proteins) 0.236
Progen2 Basefoundation model0.378mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.371Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.131Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.149Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.156
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.208Spearman (Activity assays: mean over proteins) 0.396Spearman (Binding assays: mean over proteins) 0.294Spearman (Expression assays: mean over proteins) 0.437Spearman (Organismal fitness assays: mean over proteins) 0.381Spearman (Stability assays: mean over proteins) 0.383Spearman (High MSA depth proteins: mean over proteins) 0.421Spearman (Low MSA depth proteins: mean over proteins) 0.327Spearman (Medium MSA depth proteins: mean over proteins) 0.379Spearman (Human proteins: mean over proteins) 0.422Spearman (Other eukaryote proteins: mean over proteins) 0.422Spearman (Prokaryote proteins: mean over proteins) 0.333Spearman (Virus proteins: mean over proteins) 0.316
ESM-1v (single)foundation model0.374mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.375Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.188Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.177Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.146
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.209Spearman (Activity assays: mean over proteins) 0.396Spearman (Binding assays: mean over proteins) 0.268Spearman (Expression assays: mean over proteins) 0.405Spearman (Organismal fitness assays: mean over proteins) 0.361Spearman (Stability assays: mean over proteins) 0.437Spearman (High MSA depth proteins: mean over proteins) 0.47Spearman (Low MSA depth proteins: mean over proteins) 0.289Spearman (Medium MSA depth proteins: mean over proteins) 0.373Spearman (Human proteins: mean over proteins) 0.427Spearman (Other eukaryote proteins: mean over proteins) 0.433Spearman (Prokaryote proteins: mean over proteins) 0.385Spearman (Virus proteins: mean over proteins) 0.258
Tranception L no retrievalfoundation model0.374mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.363Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.171Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.294Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.26
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.334Spearman (Activity assays: mean over proteins) 0.401Spearman (Binding assays: mean over proteins) 0.288Spearman (Expression assays: mean over proteins) 0.413Spearman (Organismal fitness assays: mean over proteins) 0.387Spearman (Stability assays: mean over proteins) 0.381Spearman (High MSA depth proteins: mean over proteins) 0.414Spearman (Low MSA depth proteins: mean over proteins) 0.332Spearman (Medium MSA depth proteins: mean over proteins) 0.379Spearman (Human proteins: mean over proteins) 0.391Spearman (Other eukaryote proteins: mean over proteins) 0.394Spearman (Prokaryote proteins: mean over proteins) 0.354Spearman (Virus proteins: mean over proteins) 0.404
RITA XLfoundation model0.373mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.357Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.141Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.148Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.16
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.233Spearman (Activity assays: mean over proteins) 0.366Spearman (Binding assays: mean over proteins) 0.302Spearman (Expression assays: mean over proteins) 0.414Spearman (Organismal fitness assays: mean over proteins) 0.384Spearman (Stability assays: mean over proteins) 0.398Spearman (High MSA depth proteins: mean over proteins) 0.412Spearman (Low MSA depth proteins: mean over proteins) 0.3Spearman (Medium MSA depth proteins: mean over proteins) 0.39Spearman (Human proteins: mean over proteins) 0.396Spearman (Other eukaryote proteins: mean over proteins) 0.399Spearman (Prokaryote proteins: mean over proteins) 0.346Spearman (Virus proteins: mean over proteins) 0.394
Wavenet0.373mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.357Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.203Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.235Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.219
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.293Spearman (Activity assays: mean over proteins) 0.379Spearman (Binding assays: mean over proteins) 0.325Spearman (Expression assays: mean over proteins) 0.35Spearman (Organismal fitness assays: mean over proteins) 0.364Spearman (Stability assays: mean over proteins) 0.449Spearman (High MSA depth proteins: mean over proteins) 0.455Spearman (Low MSA depth proteins: mean over proteins) 0.277Spearman (Medium MSA depth proteins: mean over proteins) 0.39Spearman (Human proteins: mean over proteins) 0.393Spearman (Other eukaryote proteins: mean over proteins) 0.425Spearman (Prokaryote proteins: mean over proteins) 0.406Spearman (Virus proteins: mean over proteins) 0.34
CARP (640M)foundation model0.369mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.391Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.213Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.172Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.159
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.162Spearman (Activity assays: mean over proteins) 0.395Spearman (Binding assays: mean over proteins) 0.273Spearman (Expression assays: mean over proteins) 0.397Spearman (Organismal fitness assays: mean over proteins) 0.366Spearman (Stability assays: mean over proteins) 0.412Spearman (High MSA depth proteins: mean over proteins) 0.424Spearman (Low MSA depth proteins: mean over proteins) 0.331Spearman (Medium MSA depth proteins: mean over proteins) 0.374Spearman (Human proteins: mean over proteins) 0.417Spearman (Other eukaryote proteins: mean over proteins) 0.395Spearman (Prokaryote proteins: mean over proteins) 0.381Spearman (Virus proteins: mean over proteins) 0.284
RITA Lfoundation model0.366mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.349Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.139Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.143Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.149
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.21Spearman (Activity assays: mean over proteins) 0.359Spearman (Binding assays: mean over proteins) 0.29Spearman (Expression assays: mean over proteins) 0.42Spearman (Organismal fitness assays: mean over proteins) 0.378Spearman (Stability assays: mean over proteins) 0.383Spearman (High MSA depth proteins: mean over proteins) 0.402Spearman (Low MSA depth proteins: mean over proteins) 0.301Spearman (Medium MSA depth proteins: mean over proteins) 0.379Spearman (Human proteins: mean over proteins) 0.396Spearman (Other eukaryote proteins: mean over proteins) 0.399Spearman (Prokaryote proteins: mean over proteins) 0.315Spearman (Virus proteins: mean over proteins) 0.384
Progen3 762mfoundation model0.364mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.355Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.166Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.158Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.143
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.186Spearman (Activity assays: mean over proteins) 0.376Spearman (Binding assays: mean over proteins) 0.296Spearman (Expression assays: mean over proteins) 0.386Spearman (Organismal fitness assays: mean over proteins) 0.373Spearman (Stability assays: mean over proteins) 0.386Spearman (High MSA depth proteins: mean over proteins) 0.42Spearman (Low MSA depth proteins: mean over proteins) 0.29Spearman (Medium MSA depth proteins: mean over proteins) 0.368Spearman (Human proteins: mean over proteins) 0.385Spearman (Other eukaryote proteins: mean over proteins) 0.368Spearman (Prokaryote proteins: mean over proteins) 0.362Spearman (Virus proteins: mean over proteins) 0.369
xTrimoPGLM-100B-int4foundation model0.364mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.355Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.177Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.276Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.232
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.313Spearman (Activity assays: mean over proteins) 0.378Spearman (Binding assays: mean over proteins) 0.259Spearman (Expression assays: mean over proteins) 0.38Spearman (Organismal fitness assays: mean over proteins) 0.355Spearman (Stability assays: mean over proteins) 0.45Spearman (High MSA depth proteins: mean over proteins) 0.43Spearman (Low MSA depth proteins: mean over proteins) 0.314Spearman (Medium MSA depth proteins: mean over proteins) 0.391Spearman (Human proteins: mean over proteins) 0.363Spearman (Other eukaryote proteins: mean over proteins) 0.45Spearman (Prokaryote proteins: mean over proteins) 0.422Spearman (Virus proteins: mean over proteins) 0.36
Site-IndependentBaseline0.359mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.337Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.24Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.241Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.273
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.35Spearman (Activity assays: mean over proteins) 0.369Spearman (Binding assays: mean over proteins) 0.344Spearman (Expression assays: mean over proteins) 0.343Spearman (Organismal fitness assays: mean over proteins) 0.383Spearman (Stability assays: mean over proteins) 0.358Spearman (High MSA depth proteins: mean over proteins) 0.317Spearman (Low MSA depth proteins: mean over proteins) 0.427Spearman (Medium MSA depth proteins: mean over proteins) 0.376Spearman (Human proteins: mean over proteins) 0.38Spearman (Other eukaryote proteins: mean over proteins) 0.389Spearman (Prokaryote proteins: mean over proteins) 0.318Spearman (Virus proteins: mean over proteins) 0.375
RITA Mfoundation model0.350mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.338Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.115Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.141Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.162
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.222Spearman (Activity assays: mean over proteins) 0.352Spearman (Binding assays: mean over proteins) 0.273Spearman (Expression assays: mean over proteins) 0.405Spearman (Organismal fitness assays: mean over proteins) 0.374Spearman (Stability assays: mean over proteins) 0.348Spearman (High MSA depth proteins: mean over proteins) 0.39Spearman (Low MSA depth proteins: mean over proteins) 0.286Spearman (Medium MSA depth proteins: mean over proteins) 0.359Spearman (Human proteins: mean over proteins) 0.379Spearman (Other eukaryote proteins: mean over proteins) 0.367Spearman (Prokaryote proteins: mean over proteins) 0.302Spearman (Virus proteins: mean over proteins) 0.375
Tranception M no retrievalfoundation model0.349mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.333Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.144Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.114Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.139
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.21Spearman (Activity assays: mean over proteins) 0.349Spearman (Binding assays: mean over proteins) 0.284Spearman (Expression assays: mean over proteins) 0.406Spearman (Organismal fitness assays: mean over proteins) 0.364Spearman (Stability assays: mean over proteins) 0.342Spearman (High MSA depth proteins: mean over proteins) 0.378Spearman (Low MSA depth proteins: mean over proteins) 0.269Spearman (Medium MSA depth proteins: mean over proteins) 0.358Spearman (Human proteins: mean over proteins) 0.38Spearman (Other eukaryote proteins: mean over proteins) 0.357Spearman (Prokaryote proteins: mean over proteins) 0.303Spearman (Virus proteins: mean over proteins) 0.34
Progen3 339mfoundation model0.347mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.335Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.16Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.14Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.137
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.189Spearman (Activity assays: mean over proteins) 0.345Spearman (Binding assays: mean over proteins) 0.294Spearman (Expression assays: mean over proteins) 0.38Spearman (Organismal fitness assays: mean over proteins) 0.355Spearman (Stability assays: mean over proteins) 0.359Spearman (High MSA depth proteins: mean over proteins) 0.392Spearman (Low MSA depth proteins: mean over proteins) 0.253Spearman (Medium MSA depth proteins: mean over proteins) 0.355Spearman (Human proteins: mean over proteins) 0.357Spearman (Other eukaryote proteins: mean over proteins) 0.341Spearman (Prokaryote proteins: mean over proteins) 0.354Spearman (Virus proteins: mean over proteins) 0.347
Unirep evotunedfoundation model0.347mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.32Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.155Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.244Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.236
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.294Spearman (Activity assays: mean over proteins) 0.355Spearman (Binding assays: mean over proteins) 0.305Spearman (Expression assays: mean over proteins) 0.365Spearman (Organismal fitness assays: mean over proteins) 0.345Spearman (Stability assays: mean over proteins) 0.366Spearman (High MSA depth proteins: mean over proteins) 0.376Spearman (Low MSA depth proteins: mean over proteins) 0.322Spearman (Medium MSA depth proteins: mean over proteins) 0.345Spearman (Human proteins: mean over proteins) 0.357Spearman (Other eukaryote proteins: mean over proteins) 0.378Spearman (Prokaryote proteins: mean over proteins) 0.331Spearman (Virus proteins: mean over proteins) 0.348
xTrimoPGLM-1B-CLMfoundation model0.343mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.319Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.18Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.126Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.12
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.166Spearman (Activity assays: mean over proteins) 0.347Spearman (Binding assays: mean over proteins) 0.296Spearman (Expression assays: mean over proteins) 0.4Spearman (Organismal fitness assays: mean over proteins) 0.336Spearman (Stability assays: mean over proteins) 0.333Spearman (High MSA depth proteins: mean over proteins) 0.37Spearman (Low MSA depth proteins: mean over proteins) 0.293Spearman (Medium MSA depth proteins: mean over proteins) 0.337Spearman (Human proteins: mean over proteins) 0.382Spearman (Other eukaryote proteins: mean over proteins) 0.354Spearman (Prokaryote proteins: mean over proteins) 0.301Spearman (Virus proteins: mean over proteins) 0.27
Progen2 Sfoundation model0.336mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.328Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.114Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.117Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.123
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.187Spearman (Activity assays: mean over proteins) 0.333Spearman (Binding assays: mean over proteins) 0.275Spearman (Expression assays: mean over proteins) 0.384Spearman (Organismal fitness assays: mean over proteins) 0.338Spearman (Stability assays: mean over proteins) 0.349Spearman (High MSA depth proteins: mean over proteins) 0.39Spearman (Low MSA depth proteins: mean over proteins) 0.293Spearman (Medium MSA depth proteins: mean over proteins) 0.321Spearman (Human proteins: mean over proteins) 0.385Spearman (Other eukaryote proteins: mean over proteins) 0.358Spearman (Prokaryote proteins: mean over proteins) 0.291Spearman (Virus proteins: mean over proteins) 0.271
CARP (76M)foundation model0.328mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.336Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.206Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.115Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.124
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.127Spearman (Activity assays: mean over proteins) 0.342Spearman (Binding assays: mean over proteins) 0.282Spearman (Expression assays: mean over proteins) 0.369Spearman (Organismal fitness assays: mean over proteins) 0.271Spearman (Stability assays: mean over proteins) 0.376Spearman (High MSA depth proteins: mean over proteins) 0.403Spearman (Low MSA depth proteins: mean over proteins) 0.254Spearman (Medium MSA depth proteins: mean over proteins) 0.302Spearman (Human proteins: mean over proteins) 0.388Spearman (Other eukaryote proteins: mean over proteins) 0.366Spearman (Prokaryote proteins: mean over proteins) 0.301Spearman (Virus proteins: mean over proteins) 0.157
ESM2 (35M)foundation model0.321mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.306Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.245Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.136Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.152
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.229Spearman (Activity assays: mean over proteins) 0.314Spearman (Binding assays: mean over proteins) 0.291Spearman (Expression assays: mean over proteins) 0.343Spearman (Organismal fitness assays: mean over proteins) 0.217Spearman (Stability assays: mean over proteins) 0.439Spearman (High MSA depth proteins: mean over proteins) 0.448Spearman (Low MSA depth proteins: mean over proteins) 0.247Spearman (Medium MSA depth proteins: mean over proteins) 0.271Spearman (Human proteins: mean over proteins) 0.371Spearman (Other eukaryote proteins: mean over proteins) 0.408Spearman (Prokaryote proteins: mean over proteins) 0.315Spearman (Virus proteins: mean over proteins) 0.12
Progen3 219mfoundation model0.318mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.304Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.148Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.139Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.145
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.194Spearman (Activity assays: mean over proteins) 0.31Spearman (Binding assays: mean over proteins) 0.293Spearman (Expression assays: mean over proteins) 0.347Spearman (Organismal fitness assays: mean over proteins) 0.335Spearman (Stability assays: mean over proteins) 0.305Spearman (High MSA depth proteins: mean over proteins) 0.332Spearman (Low MSA depth proteins: mean over proteins) 0.246Spearman (Medium MSA depth proteins: mean over proteins) 0.332Spearman (Human proteins: mean over proteins) 0.319Spearman (Other eukaryote proteins: mean over proteins) 0.288Spearman (Prokaryote proteins: mean over proteins) 0.335Spearman (Virus proteins: mean over proteins) 0.326
MULANfoundation model0.317mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.292Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.23Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.079Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.11
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.17Spearman (Activity assays: mean over proteins) 0.283Spearman (Binding assays: mean over proteins) 0.326Spearman (Expression assays: mean over proteins) 0.383Spearman (Organismal fitness assays: mean over proteins) 0.225Spearman (Stability assays: mean over proteins) 0.369Spearman (High MSA depth proteins: mean over proteins) 0.338Spearman (Low MSA depth proteins: mean over proteins) 0.273Spearman (Medium MSA depth proteins: mean over proteins) 0.291Spearman (Human proteins: mean over proteins) 0.343Spearman (Other eukaryote proteins: mean over proteins) 0.315Spearman (Prokaryote proteins: mean over proteins) 0.313Spearman (Virus proteins: mean over proteins) 0.167
RITA Sfoundation model0.305mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.287Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.114Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.104Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.122
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.19Spearman (Activity assays: mean over proteins) 0.294Spearman (Binding assays: mean over proteins) 0.275Spearman (Expression assays: mean over proteins) 0.336Spearman (Organismal fitness assays: mean over proteins) 0.329Spearman (Stability assays: mean over proteins) 0.289Spearman (High MSA depth proteins: mean over proteins) 0.332Spearman (Low MSA depth proteins: mean over proteins) 0.249Spearman (Medium MSA depth proteins: mean over proteins) 0.305Spearman (Human proteins: mean over proteins) 0.331Spearman (Other eukaryote proteins: mean over proteins) 0.299Spearman (Prokaryote proteins: mean over proteins) 0.238Spearman (Virus proteins: mean over proteins) 0.344
Tranception S no retrievalfoundation model0.303mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.279Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.116Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.107Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.128
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.189Spearman (Activity assays: mean over proteins) 0.288Spearman (Binding assays: mean over proteins) 0.286Spearman (Expression assays: mean over proteins) 0.349Spearman (Organismal fitness assays: mean over proteins) 0.321Spearman (Stability assays: mean over proteins) 0.27Spearman (High MSA depth proteins: mean over proteins) 0.315Spearman (Low MSA depth proteins: mean over proteins) 0.235Spearman (Medium MSA depth proteins: mean over proteins) 0.304Spearman (Human proteins: mean over proteins) 0.318Spearman (Other eukaryote proteins: mean over proteins) 0.283Spearman (Prokaryote proteins: mean over proteins) 0.263Spearman (Virus proteins: mean over proteins) 0.304
Progen3 112mfoundation model0.282mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.265Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.103Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.121Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.138
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.199Spearman (Activity assays: mean over proteins) 0.273Spearman (Binding assays: mean over proteins) 0.301Spearman (Expression assays: mean over proteins) 0.302Spearman (Organismal fitness assays: mean over proteins) 0.301Spearman (Stability assays: mean over proteins) 0.233Spearman (High MSA depth proteins: mean over proteins) 0.272Spearman (Low MSA depth proteins: mean over proteins) 0.221Spearman (Medium MSA depth proteins: mean over proteins) 0.291Spearman (Human proteins: mean over proteins) 0.262Spearman (Other eukaryote proteins: mean over proteins) 0.248Spearman (Prokaryote proteins: mean over proteins) 0.295Spearman (Virus proteins: mean over proteins) 0.301
CARP (38M)foundation model0.280mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.279Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.173Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.106Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.126
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.143Spearman (Activity assays: mean over proteins) 0.285Spearman (Binding assays: mean over proteins) 0.268Spearman (Expression assays: mean over proteins) 0.312Spearman (Organismal fitness assays: mean over proteins) 0.218Spearman (Stability assays: mean over proteins) 0.314Spearman (High MSA depth proteins: mean over proteins) 0.354Spearman (Low MSA depth proteins: mean over proteins) 0.206Spearman (Medium MSA depth proteins: mean over proteins) 0.24Spearman (Human proteins: mean over proteins) 0.322Spearman (Other eukaryote proteins: mean over proteins) 0.307Spearman (Prokaryote proteins: mean over proteins) 0.253Spearman (Virus proteins: mean over proteins) 0.127
ProteinMPNNfoundation model0.257mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.292Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.26Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.174Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.183
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.278Spearman (Activity assays: mean over proteins) 0.197Spearman (Binding assays: mean over proteins) 0.163Spearman (Expression assays: mean over proteins) 0.198Spearman (Organismal fitness assays: mean over proteins) 0.164Spearman (Stability assays: mean over proteins) 0.565Spearman (High MSA depth proteins: mean over proteins) 0.439Spearman (Low MSA depth proteins: mean over proteins) 0.187Spearman (Medium MSA depth proteins: mean over proteins) 0.271Spearman (Human proteins: mean over proteins) 0.284Spearman (Other eukaryote proteins: mean over proteins) 0.394Spearman (Prokaryote proteins: mean over proteins) 0.348Spearman (Virus proteins: mean over proteins) 0.262
xTrimoPGLM-3B-CLMfoundation model0.233mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.205Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.1Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.009Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.028
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.05Spearman (Activity assays: mean over proteins) 0.214Spearman (Binding assays: mean over proteins) 0.249Spearman (Expression assays: mean over proteins) 0.27Spearman (Organismal fitness assays: mean over proteins) 0.236Spearman (Stability assays: mean over proteins) 0.196Spearman (High MSA depth proteins: mean over proteins) 0.243Spearman (Low MSA depth proteins: mean over proteins) 0.201Spearman (Medium MSA depth proteins: mean over proteins) 0.215Spearman (Human proteins: mean over proteins) 0.283Spearman (Other eukaryote proteins: mean over proteins) 0.219Spearman (Prokaryote proteins: mean over proteins) 0.134Spearman (Virus proteins: mean over proteins) 0.19
ESM2 (8M)foundation model0.226mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.203Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.14Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.11Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.126
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.195Spearman (Activity assays: mean over proteins) 0.201Spearman (Binding assays: mean over proteins) 0.26Spearman (Expression assays: mean over proteins) 0.266Spearman (Organismal fitness assays: mean over proteins) 0.14Spearman (Stability assays: mean over proteins) 0.262Spearman (High MSA depth proteins: mean over proteins) 0.262Spearman (Low MSA depth proteins: mean over proteins) 0.2Spearman (Medium MSA depth proteins: mean over proteins) 0.177Spearman (Human proteins: mean over proteins) 0.241Spearman (Other eukaryote proteins: mean over proteins) 0.248Spearman (Prokaryote proteins: mean over proteins) 0.201Spearman (Virus proteins: mean over proteins) 0.09
Unirepfoundation model0.190mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.176Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.073Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.109Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.136
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.191Spearman (Activity assays: mean over proteins) 0.182Spearman (Binding assays: mean over proteins) 0.202Spearman (Expression assays: mean over proteins) 0.216Spearman (Organismal fitness assays: mean over proteins) 0.139Spearman (Stability assays: mean over proteins) 0.21Spearman (High MSA depth proteins: mean over proteins) 0.209Spearman (Low MSA depth proteins: mean over proteins) 0.183Spearman (Medium MSA depth proteins: mean over proteins) 0.158Spearman (Human proteins: mean over proteins) 0.215Spearman (Other eukaryote proteins: mean over proteins) 0.233Spearman (Prokaryote proteins: mean over proteins) 0.152Spearman (Virus proteins: mean over proteins) 0.066
ProtGPT2foundation model0.188mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.181Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.14Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.048Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.036
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.078Spearman (Activity assays: mean over proteins) 0.176Spearman (Binding assays: mean over proteins) 0.149Spearman (Expression assays: mean over proteins) 0.193Spearman (Organismal fitness assays: mean over proteins) 0.166Spearman (Stability assays: mean over proteins) 0.257Spearman (High MSA depth proteins: mean over proteins) 0.252Spearman (Low MSA depth proteins: mean over proteins) 0.188Spearman (Medium MSA depth proteins: mean over proteins) 0.171Spearman (Human proteins: mean over proteins) 0.244Spearman (Other eukaryote proteins: mean over proteins) 0.242Spearman (Prokaryote proteins: mean over proteins) 0.134Spearman (Virus proteins: mean over proteins) 0.138
CARP (600K)foundation model0.106mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.108Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.029Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.045Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.076
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.096Spearman (Activity assays: mean over proteins) 0.112Spearman (Binding assays: mean over proteins) 0.084Spearman (Expression assays: mean over proteins) 0.171Spearman (Organismal fitness assays: mean over proteins) 0.059Spearman (Stability assays: mean over proteins) 0.105Spearman (High MSA depth proteins: mean over proteins) 0.1Spearman (Low MSA depth proteins: mean over proteins) 0.101Spearman (Medium MSA depth proteins: mean over proteins) 0.085Spearman (Human proteins: mean over proteins) 0.122Spearman (Other eukaryote proteins: mean over proteins) 0.086Spearman (Prokaryote proteins: mean over proteins) 0.075Spearman (Virus proteins: mean over proteins) 0.055
xTrimoPGLM-7B-CLMfoundation model0.102mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)Spearman (variants with 1 substitution: mean over protein and selection-type groups) 0.085Spearman (variants with 2 substitutions: mean over protein and selection-type groups) 0.039Spearman (variants with 3 substitutions: mean over protein and selection-type groups) 0.01Spearman (variants with 4 substitutions: mean over protein and selection-type groups) 0.029
13 more valuesSpearman (variants with 5 or more substitutions: mean over protein and selection-type groups) 0.081Spearman (Activity assays: mean over proteins) 0.116Spearman (Binding assays: mean over proteins) 0.154Spearman (Expression assays: mean over proteins) 0.078Spearman (Organismal fitness assays: mean over proteins) 0.061Spearman (Stability assays: mean over proteins) 0.099Spearman (High MSA depth proteins: mean over proteins) 0.117Spearman (Low MSA depth proteins: mean over proteins) 0.082Spearman (Medium MSA depth proteins: mean over proteins) 0.072Spearman (Human proteins: mean over proteins) 0.13Spearman (Other eukaryote proteins: mean over proteins) 0.115Spearman (Prokaryote proteins: mean over proteins) 0.044Spearman (Virus proteins: mean over proteins) 0.012
Show all 97 rowsShow the top 10 rows only
Caveats and method
  • Averages over proteins do not predict performance on a single protein of interest.
  • Leaderboard rows were computed by the ProteinGym maintainers with their scoring scripts (origin unreported); no Rewire run on the full track.
  • Assays include multiple substitutions; Depth_1 is the singles-only column.
  • Bootstrap standard errors are relative to the top model (the top row prints 0.0).
  • Some leaderboard models were developed by ProteinGym's authors (for example EVE, Tranception and TranceptEVE).
  • Assays come from proteins of many organisms; results for human proteins alone are not given in this summary.
  • Transcribed from the source; no reproduction by Rewire and no human scientific review.

Protocol: ProteinGym v1.3 zero-shot DMS substitutions

Not covered yet

  • Benchmarks report averages over proteins; performance on a single protein varies and is not predicted by the averages.
  • ProteinGym supervised DMS results are stored as tasks from the 2023 paper, not as protocols, so they cannot be linked here; the supervised summaries at commit 144fe22 were not extracted.
  • ProteinGym zero-shot DMS AUC, MCC, NDCG and top-recall summaries at commit 144fe22 were not extracted.
  • Livesey and Marsh rank scores are relative to the 97 compared predictors; per-protein Spearman values are in the figshare deposit, not retrieved.
  • No Rewire run of a full DMS track exists; the ProteinGym rows are leaderboard values.
  • Qualified human scientific review is outstanding; automated transcription does not establish replication.

Contribute evidence or propose a correction

Question, sources and review

Who this is for, setting and exclusions

Choose a predictor, or a short list, to rank substitutions in the target protein before or alongside an assay, given whether a deep alignment, a structure or labelled data are available.

Who this is for
  • Researchers planning or interpreting deep mutational scans
  • Protein scientists choosing variants for functional assays
  • Computational biologists selecting a zero-shot variant effect predictor
Biological setting
Zero-shot scoring of amino acid substitutions benchmarked against DMS assays: ProteinGym at commit 144fe22 (217 substitution assays across many organisms) and Livesey and Marsh 2025 (36 human DMS sets with ClinVar and gnomAD variants removed).
Research setting
Research use. Agreement with DMS readouts does not establish clinical pathogenicity.

Outside this use case

  • Clinical pathogenicity classification (see the PP3/BP4 and rare-disease use cases)
  • Folding stability alone (see the protein stability use case)
  • Supervised models trained on the target assay
  • Insertions and deletions
  • Design of new sequences
Sources, review and downloads

Automated source review · 2026-10-14 · Claude review agent; no human review claimed. Independent Claude (Opus 5.5) review agent, separate from the extraction agent that built this batch. Automated review only. Transcription, not reproduction.

Drafted by the extraction agent; reviewed in docs/reviews/vep-use-cases-2026-10-14-review.md.

Release 2026-10-22-1b7cf027e4f6 · question use-case-protein-variant-effect-prediction

Use-case input digest 99e60ea7a46185ebf28288166b0774bb6aa7fc512cb8be19b6f1ae684d18f771

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