rewirebio.iobenchmarks
Contested result

MetaSVM and ESM-1b: Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods reverses the order

  • Low severity
  • Not yet reviewed
  • Ordering reversal
  • Different tasks across studies

Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods ranks MetaSVM above ESM-1b in 2 of 2 comparisons; other studies rank ESM-1b above MetaSVM in 13 of 13.

An automatic lead, not a finding of error. The results below are shown as published, everywhere on the site, until a reviewer decides otherwise.

Which studies agree

2 papers rank ESM-1b above MetaSVM in all 13 of their comparisons. Brandes et al. 2023 ranks MetaSVM above ESM-1b in all 2 comparisons that are not ties (2 are ties).

Papers grouped by which system they rank higher: ESM-1b or MetaSVMRank ESM-1b higher: Livesey and Marsh 2025, An openly licensed benchmark…. Rank MetaSVM higher: Brandes et al. 2023 (disagrees). Mixed: none.Rank ESM-1b higherMixedRank MetaSVM higherLivesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)An openly licensedbenchmark…An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer driversBrandes et al. 2023Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods
  • Rank ESM-1b higher (2): Livesey and Marsh 2025, An openly licensed benchmark…
  • Rank MetaSVM higher (1): Brandes et al. 2023 (disagrees)
  • Mixed (0): none

Each paper sits where at least two thirds of its comparisons point; Mixed means neither model reaches two thirds. The larger, outlined dot is the paper that disagrees.

Comparisons in which each paper scores ESM-1b or MetaSVM higherBrandes et al. 2023 (disagrees): ESM-1b higher in 0, MetaSVM higher in 2, 2 ties. Livesey and Marsh 2025: ESM-1b higher in 7, MetaSVM higher in 0, 0 ties. An openly licensed benchmark…: ESM-1b higher in 6, MetaSVM higher in 0, 0 ties.Disagrees: Brandes et al. 2023Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods2 tie22 MetaSVM higher2Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)7 ESM-1b higher7An openly licensed benchmark…An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers6 ESM-1b higher6
ESM-1b higherTieMetaSVM higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Comparisons in Brandes et al. 2023 (4)
ProtocolDatasetMetricESM-1bMetaSVMHigher
ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)ClinVar missense variants scored by both ESM1b and MetaSVM (Brandes et al. 2023)AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot), unitless0.9060.903Tie
ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)ClinVar missense variants scored by both ESM1b and MetaSVM (Brandes et al. 2023)AUROC (global ROC-AUC over the variants both methods score; zero-shot), unitless0.9060.91Tie
HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)HGMD/gnomAD missense variants scored by both ESM1b and MetaSVM (Brandes et al. 2023)AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot), unitless0.9050.965MetaSVM
HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)HGMD/gnomAD missense variants scored by both ESM1b and MetaSVM (Brandes et al. 2023)AUROC (global ROC-AUC over the variants both methods score; zero-shot), unitless0.8940.954MetaSVM
Comparisons in Livesey and Marsh 2025 (7)
ProtocolDatasetMetricESM-1bMetaSVMHigher
Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missenseLivesey and Marsh 2025 clinical set: ClinVar pathogenic versus gnomAD v4.1 missense (819 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, per-protein AUROC on shared variants, ClinVar P/LP versus gnomAD v4.1 missense, proteins with at least 10 of each), percent54.345.5ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets), percent6539ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against the five top-ranked VEPs (column top_5_winrate; the five are not listed in the table), |Spearman| with DMS on shared variants, 36 human DMS sets), percent14.78.13ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only), percent62.439.4ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only), percent6738.5ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only), percent64.539ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS, SNV-accessible substitutions, missing predictions filled with the VEP's most benign score), percent65.939.9ESM-1b
Comparisons in An openly licensed benchmark… (6)
ProtocolDatasetMetricESM-1bMetaSVMHigher
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, all genes), unitless0.8420.762ESM-1b
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, all genes), unitless0.6410.507ESM-1b
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, oncogenes (gain of function)), unitless0.8410.766ESM-1b
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, oncogenes (gain of function)), unitless0.7190.563ESM-1b
CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, tumour suppressors (loss of function)), unitless0.8580.794ESM-1b
CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, tumour suppressors (loss of function)), unitless0.5940.5ESM-1b

What disagrees

Other studies
rank ESM-1b above MetaSVM in 13 of 13 comparisons
This study
ranks MetaSVM above ESM-1b in 2 of 2 comparisons
Compared
MetaSVM, ESM-1b
Study that disagrees
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods
Other studies
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers, OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role), Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML), Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)
Rule
Ordering reversal; different tasks across studies
Model identity
Matched across studies partly through links not yet reviewed

The compared numbers

Each value links to its result record and source. Compare values within one protocol; the rule compares rankings, not raw values across protocols.

In the study that disagrees (4)
StudyToolProtocol or benchmarkMetricValue
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)ESM1b (Brandes et al. 2023 clinical benchmarks)HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.905
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)ESM1b (Brandes et al. 2023 clinical benchmarks)HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)AUROC (global ROC-AUC over the variants both methods score; zero-shot)0.894
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)MetaSVM (Brandes et al. 2023 head-to-head comparison)HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.965
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)MetaSVM (Brandes et al. 2023 head-to-head comparison)HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)AUROC (global ROC-AUC over the variants both methods score; zero-shot)0.954
In the other studies (26)
StudyToolProtocol or benchmarkMetricValue
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, all genes)0.641
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, all genes)0.842
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, oncogenes (gain of function))0.719
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, oncogenes (gain of function))0.841
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, tumour suppressors (loss of function))0.594
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)ESM1b rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, tumour suppressors (loss of function))0.858
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, all genes)0.507
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, all genes)0.762
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, oncogenes (gain of function))0.563
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, oncogenes (gain of function))0.766
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Average precision (CGC missense, tumour suppressors (loss of function))0.5
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers; OncoCal repository, tables/tool_performance.tsv (per-tool AUROC and AUPRC by gene role)MetaSVM rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, tumour suppressors (loss of function))0.794
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missensePairwise win rate (average pairwise win rate against all other VEPs, per-protein AUROC on shared variants, ClinVar P/LP versus gnomAD v4.1 missense, proteins with at least 10 of each)54.3
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missensePairwise win rate (average pairwise win rate against all other VEPs, per-protein AUROC on shared variants, ClinVar P/LP versus gnomAD v4.1 missense, proteins with at least 10 of each)45.5
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets)65
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against the five top-ranked VEPs (column top_5_winrate; the five are not listed in the table), |Spearman| with DMS on shared variants, 36 human DMS sets)14.7
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets)39
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against the five top-ranked VEPs (column top_5_winrate; the five are not listed in the table), |Spearman| with DMS on shared variants, 36 human DMS sets)8.13
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only)62.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only)39.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only)67
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only)38.5
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only)64.5
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ESM-1b (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS, SNV-accessible substitutions, missing predictions filled with the VEP's most benign score)65.9
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS, SNV-accessible substitutions, missing predictions filled with the VEP's most benign score)39.9
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MetaSVM (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only)39

Follow-up

Current state: Not yet reviewed.

No one has reviewed this finding yet.

How to help resolve this

If you know why these studies disagree, for example a different population, metric or preprocessing step, or you have a corrected value, tell us through the contribution form. A reviewer checks every submission against its source before anything changes, and the step is added to the follow-up above.

Finding discrepancy-4099c0afb300547c · All contested results · How findings are made and followed up