rewirebio.iobenchmarks
Contested result

MutFormer and PolyPhen-2: An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers reverses the order

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

An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers ranks PolyPhen-2 above MutFormer in 6 of 6 comparisons; other studies rank MutFormer above PolyPhen-2 in 6 of 6.

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

Livesey and Marsh 2025 ranks MutFormer above PolyPhen-2 in all 6 of its comparisons. An openly licensed benchmark… ranks PolyPhen-2 above MutFormer in all 6 of its comparisons.

Papers grouped by which system they rank higher: MutFormer or PolyPhen-2Rank MutFormer higher: Livesey and Marsh 2025. Rank PolyPhen-2 higher: An openly licensed benchmark… (disagrees). Mixed: none.Rank MutFormer higherMixedRank PolyPhen-2 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 drivers
  • Rank MutFormer higher (1): Livesey and Marsh 2025
  • Rank PolyPhen-2 higher (1): An openly licensed benchmark… (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 MutFormer or PolyPhen-2 higherAn openly licensed benchmark… (disagrees): MutFormer higher in 0, PolyPhen-2 higher in 6, 0 ties. Livesey and Marsh 2025: MutFormer higher in 6, PolyPhen-2 higher in 0, 0 ties.Disagrees: An openly licensed benchmark…An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers6 PolyPhen-2 higher6Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)6 MutFormer higher6
MutFormer higherTiePolyPhen-2 higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Papers compared (2)
PaperRoleRanks MutFormer higherRanks PolyPhen-2 higherTies
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers and 1 more record · DOIDisagrees060
Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and 1 more record · DOIAgrees600
Comparisons in An openly licensed benchmark… (6)
ProtocolDatasetMetricMutFormerPolyPhen-2Higher
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), unitless0.6930.826PolyPhen-2
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), unitless0.4460.55PolyPhen-2
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)), unitless0.7680.82PolyPhen-2
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)), unitless0.5820.602PolyPhen-2
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)), unitless0.6550.852PolyPhen-2
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)), unitless0.2860.482PolyPhen-2
Comparisons in Livesey and Marsh 2025 (6)
ProtocolDatasetMetricMutFormerPolyPhen-2Higher
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), percent71.448.3MutFormer
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), percent17.28.47MutFormer
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), percent74.746.2MutFormer
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), percent68.950MutFormer
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), percent71.448.4MutFormer
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), percent70.549.7MutFormer

What disagrees

Other studies
rank MutFormer above PolyPhen-2 in 6 of 6 comparisons
This study
ranks PolyPhen-2 above MutFormer in 6 of 6 comparisons
Compared
MutFormer, PolyPhen-2
Study that disagrees
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)
Other studies
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 (12)
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)MutFormer 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)0.446
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)MutFormer rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, all genes)0.693
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)MutFormer 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))0.582
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)MutFormer 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))0.768
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)MutFormer 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))0.286
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)MutFormer 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))0.655
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)Polyphen2_HVAR 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)0.55
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)Polyphen2_HVAR rank score, dbNSFP 5.3.1a (Lee 2026)CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)AUROC (CGC missense, all genes)0.826
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)Polyphen2_HVAR 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))0.602
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)Polyphen2_HVAR 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))0.82
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)Polyphen2_HVAR 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))0.482
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)Polyphen2_HVAR 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))0.852
In the other studies (12)
StudyToolProtocol or benchmarkMetricValue
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)71.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)17.2
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)48.3
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)8.47
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)74.7
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)46.2
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)68.9
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)50
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)70.5
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)49.7
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)MutFormer (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)71.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)PolyPhen2_HumVar (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)48.4

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-c5cb6005f65e5c0d · All contested results · How findings are made and followed up