Contested result

CADD and PolyPhen-2: Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) reverses the order

Low severity
Not yet reviewed
Ordering reversal
Different tasks across studies

Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) ranks PolyPhen-2 above CADD in 6 of 6 comparisons; other studies rank CADD above PolyPhen-2 in 11 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

4 papers rank CADD above PolyPhen-2 in 11 of their 22 comparisons and PolyPhen-2 higher in 2; 9 are ties. Livesey and Marsh 2025 ranks PolyPhen-2 above CADD in all 6 of its comparisons.

Rank CADD higher (2): Comprehensive assessment…, An openly licensed benchmark…
Rank PolyPhen-2 higher (1): Livesey and Marsh 2025 (disagrees)
Mixed (2): Clinical likelihood ratios and balanced…, ProteinGym AMFR assay-level Spearman…

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.

CADD higherTiePolyPhen-2 higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.

Papers compared (5)
Paper	Role	Ranks CADD higher	Ranks PolyPhen-2 higher	Ties
Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and 1 more record · DOI	Disagrees	0	6	0
Comprehensive assessment of computational algorithms in predicting cancer driver mutations and 4 more records · DOI	Agrees	4	0	6
An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers and 1 more record · DOI	Agrees	4	0	2
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes and 1 more record · DOI	Agrees	3	2	0
ProteinGym AMFR assay-level Spearman comparison and 4 more records · Repository	Agrees	0	0	1

Comparisons in Livesey and Marsh 2025 (6)

Protocol	Dataset	Metric	CADD	PolyPhen-2	Higher
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, all 36 DMS sets	Livesey 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), percent	40.3	48.3	PolyPhen-2
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, all 36 DMS sets	Livesey 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), percent	2.89	8.47	PolyPhen-2
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, direct assays only	Livesey 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), percent	39	46.2	PolyPhen-2
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, indirect assays only	Livesey 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), percent	41.2	50	PolyPhen-2
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, SNV-accessible substitutions only	Livesey 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), percent	40.3	48.4	PolyPhen-2
Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, SNV-accessible substitutions with gaps filled	Livesey 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), percent	42	49.7	PolyPhen-2

Comparisons in Comprehensive assessment… (10)

Protocol	Dataset	Metric	CADD	PolyPhen-2	Higher
OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	OncoKB-annotated somatic missense mutations (oncogenic, likely oncogenic and likely neutral)	Accuracy (OncoKB benchmark (positive set not stated), median-score threshold), fraction	0.64	0.63	CADD
OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	OncoKB-annotated somatic missense mutations (oncogenic, likely oncogenic and likely neutral)	Negative predictive value (OncoKB benchmark (positive set not stated), median-score threshold), fraction	0.64	0.63	CADD
OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	OncoKB-annotated somatic missense mutations (oncogenic, likely oncogenic and likely neutral)	Precision (OncoKB benchmark (positive set not stated), median-score threshold), fraction	0.64	0.62	CADD
OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	OncoKB-annotated somatic missense mutations (oncogenic, likely oncogenic and likely neutral)	Recall (OncoKB benchmark (positive set not stated), median-score threshold), fraction	0.64	0.64	Tie
OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	OncoKB-annotated somatic missense mutations (oncogenic, likely oncogenic and likely neutral)	Specificity (OncoKB benchmark (positive set not stated), median-score threshold), fraction	0.64	0.62	CADD
Cell viability drivers versus neutral, median-score threshold (Chen et al. 2020 Additional file 21)	Missense mutations with Ba/F3 and MCF10A cell viability calls (published and new)	Accuracy (cell viability drivers versus neutral, median-score threshold), fraction	0.59	0.59	Tie
Cell viability drivers versus neutral, median-score threshold (Chen et al. 2020 Additional file 21)	Missense mutations with Ba/F3 and MCF10A cell viability calls (published and new)	Negative predictive value (cell viability drivers versus neutral, median-score threshold), fraction	0.59	0.59	Tie
Cell viability drivers versus neutral, median-score threshold (Chen et al. 2020 Additional file 21)	Missense mutations with Ba/F3 and MCF10A cell viability calls (published and new)	Precision (cell viability drivers versus neutral, median-score threshold), fraction	0.59	0.59	Tie
Cell viability drivers versus neutral, median-score threshold (Chen et al. 2020 Additional file 21)	Missense mutations with Ba/F3 and MCF10A cell viability calls (published and new)	Recall (cell viability drivers versus neutral, median-score threshold), fraction	0.59	0.59	Tie
Cell viability drivers versus neutral, median-score threshold (Chen et al. 2020 Additional file 21)	Missense mutations with Ba/F3 and MCF10A cell viability calls (published and new)	Specificity (cell viability drivers versus neutral, median-score threshold), fraction	0.59	0.59	Tie

Comparisons in An openly licensed benchmark… (6)

Protocol	Dataset	Metric	CADD	PolyPhen-2	Higher
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)	Missense variants in 768 Cancer Gene Census genes with open oncogenicity labels	AUROC (CGC missense, all genes), unitless	0.826	0.826	Tie
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)	Missense variants in 768 Cancer Gene Census genes with open oncogenicity labels	Average precision (CGC missense, all genes), unitless	0.596	0.55	CADD
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)	Missense variants in 768 Cancer Gene Census genes with open oncogenicity labels	AUROC (CGC missense, oncogenes (gain of function)), unitless	0.821	0.82	Tie
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)	Missense variants in 768 Cancer Gene Census genes with open oncogenicity labels	Average precision (CGC missense, oncogenes (gain of function)), unitless	0.642	0.602	CADD
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 labels	AUROC (CGC missense, tumour suppressors (loss of function)), unitless	0.894	0.852	CADD
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 labels	Average precision (CGC missense, tumour suppressors (loss of function)), unitless	0.646	0.482	CADD

Comparisons in Clinical likelihood ratios and balanced… (5)

Protocol	Dataset	Metric	CADD	PolyPhen-2	Higher
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set), unitless	36.7	27.6	CADD
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	False negatives (Functionally deleterious BRCA1 variants called tolerated), count	0	2	CADD
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA1 functional truth set), unitless	1.1	1.28	PolyPhen-2
BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repair	False negatives (Functionally deleterious BRCA2 variants called tolerated), count	0	1	CADD
BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repair	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set), unitless	1.07	1.28	PolyPhen-2

Comparisons in ProteinGym AMFR assay-level Spearman… (1)

Protocol	Dataset	Metric	CADD	PolyPhen-2	Higher
ProteinGym clinical substitutions, supervised predictors, average AUC (commit 144fe22)	ProteinGym clinical substitution benchmark at commit 144fe22	AUROC (ProteinGym clinical substitutions, supervised clinical predictors, Average_AUC over proteins), unitless	0.905	0.896	Tie

What disagrees

Other studies: rank CADD above PolyPhen-2 in 11 of 13 comparisons
This study: ranks PolyPhen-2 above CADD in 6 of 6 comparisons

Compared: CADD, PolyPhen-2
Study that disagrees: Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML), Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)
Other studies: 9 studies
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes, Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx), Comprehensive assessment of computational algorithms in predicting cancer driver mutations, Chen et al. 2020, Additional file 10: Performance metrics of 17 algorithms, default categories, benchmark 2 (OncoKB), Chen et al. 2020, Additional file 21: Performance metrics of 33 algorithms, median-score threshold, benchmark 5 (cell viability), Chen et al. 2020, Additional file 22: Performance metrics of 17 algorithms, default categories, benchmark 5 (cell viability), Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB), 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)
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)
Study	Tool	Protocol or benchmark	Metric	Value
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, all 36 DMS sets	Pairwise win rate (average pairwise win rate against all other VEPs, \|Spearman\| with DMS on shared variants, 36 human DMS sets)	40.3
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, all 36 DMS sets	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)	2.89
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 sets	Pairwise 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 sets	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)	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)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, direct assays only	Pairwise win rate (average pairwise win rate against all other VEPs, \|Spearman\| with DMS on shared variants, direct DMS assays only)	39
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 only	Pairwise 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)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, indirect assays only	Pairwise win rate (average pairwise win rate against all other VEPs, \|Spearman\| with DMS on shared variants, indirect DMS assays only)	41.2
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, indirect assays only	Pairwise 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)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, SNV-accessible substitutions only	Pairwise win rate (average pairwise win rate against all other VEPs, \|Spearman\| with DMS on shared variants, SNV-accessible substitutions only)	40.3
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)	CADD_1.7 (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, SNV-accessible substitutions with gaps filled	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)	42
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 filled	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)	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)	PolyPhen2_HumVar (Livesey and Marsh 2025)	Livesey and Marsh 2025 DMS benchmark: pairwise \|Spearman\| win rate, SNV-accessible substitutions only	Pairwise win rate (average pairwise win rate against all other VEPs, \|Spearman\| with DMS on shared variants, SNV-accessible substitutions only)	48.4

In the other studies (29)
Study	Tool	Protocol or benchmark	Metric	Value
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_a (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set)	36.7
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_a (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA1 functional truth set)	1.1
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_a (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA2 variants called tolerated)	0
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_a (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set)	1.07
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_b (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA1 variants called tolerated)	0
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	CADD_phred_b (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA2 variants called tolerated)	0
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HDIV (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set)	27.6
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HDIV (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA1 variants called tolerated)	2
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HDIV (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA2 variants called tolerated)	1
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HVAR (Cubuk et al. 2021)	BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA1 functional truth set)	1.28
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HVAR (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	False negatives (Functionally deleterious BRCA2 variants called tolerated)	1
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)	Polyphen2_HVAR (Cubuk et al. 2021)	BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)	Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set)	1.28
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	CADD (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Accuracy (OncoKB benchmark (positive set not stated), median-score threshold)	0.64
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	CADD (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Negative predictive value (OncoKB benchmark (positive set not stated), median-score threshold)	0.64
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	CADD (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Precision (OncoKB benchmark (positive set not stated), median-score threshold)	0.64
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	CADD (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Specificity (OncoKB benchmark (positive set not stated), median-score threshold)	0.64
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	Polyphen2_HDIV (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Accuracy (OncoKB benchmark (positive set not stated), median-score threshold)	0.63
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	Polyphen2_HDIV (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Negative predictive value (OncoKB benchmark (positive set not stated), median-score threshold)	0.63
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	Polyphen2_HDIV (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Precision (OncoKB benchmark (positive set not stated), median-score threshold)	0.62
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	Polyphen2_HDIV (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Specificity (OncoKB benchmark (positive set not stated), median-score threshold)	0.62
Comprehensive assessment of computational algorithms in predicting cancer driver mutations; Chen et al. 2020, Additional file 9: Performance metrics of 33 algorithms, median-score threshold, benchmark 2 (OncoKB)	Polyphen2_HVAR (Chen et al. 2020)	OncoKB benchmark (positive set not stated), median-score threshold (Chen et al. 2020 Additional file 9)	Precision (OncoKB benchmark (positive set not stated), median-score threshold)	0.62
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)	CADD_raw 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)	0.596
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)	CADD_raw 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))	0.642
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)	CADD_raw 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))	0.646
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)	CADD_raw 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))	0.894
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, 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, 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

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