rewirebio.iobenchmarks
Contested result

Condel and SIFT: Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes and Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) disagree

  • Low severity
  • Not yet reviewed
  • two-study-conflict
  • unknown

Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes ranks SIFT above Condel in 5 of 5 comparisons; Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) ranks Condel above SIFT in 7 of 7 comparisons. No other study gives a verdict, so neither is the outlier.

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 Condel above SIFT in 7 of their 12 comparisons and SIFT higher in 5. Of those papers, Clinical likelihood ratios and balanced… ranks SIFT higher on its own (5 of 5).

Papers grouped by which system they rank higher: Condel or SIFTRank Condel higher: Livesey and Marsh 2025. Rank SIFT higher: Clinical likelihood ratios and balanced…. Mixed: none.Rank Condel higherMixedRank SIFT higherLivesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)Clinical likelihoodratios and balanced…Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes
  • Rank Condel higher (1): Livesey and Marsh 2025
  • Rank SIFT higher (1): Clinical likelihood ratios and balanced…
  • 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 Condel or SIFT higherLivesey and Marsh 2025: Condel higher in 7, SIFT higher in 0, 0 ties. Clinical likelihood ratios and balanced…: Condel higher in 0, SIFT higher in 5, 0 ties.Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)7 Condel higher7Clinical likelihood ratios and balanced…Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes5 SIFT higher5
Condel higherTieSIFT higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Comparisons in Livesey and Marsh 2025 (7)
ProtocolDatasetMetricCondelSIFTHigher
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), percent49.934.8Condel
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), percent47.539.3Condel
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), percent9.761.22Condel
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), percent45.239.9Condel
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), percent4938.8Condel
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), percent47.540.3Condel
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), percent47.841.8Condel
Comparisons in Clinical likelihood ratios and balanced… (5)
ProtocolDatasetMetricCondelSIFTHigher
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 editingBenignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set), unitless7.423.9SIFT
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 editingFalse negatives (Functionally deleterious BRCA1 variants called tolerated), count93SIFT
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 editingLikelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA1 functional truth set), unitless1.181.23SIFT
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 repairFalse negatives (Functionally deleterious BRCA2 variants called tolerated), count10SIFT
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 repairLikelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set), unitless1.051.24SIFT

What disagrees

studies
2
Compared
Condel, SIFT
Study that disagrees
Other studies
Rule
two-study-conflict; unknown
Model identity
Matched across studies partly through links not yet reviewed

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-358e3e0180d12c5d · All contested results · How findings are made and followed up