REVEL

Rare Exome Variant Ensemble Learner. An ensemble method that integrates 13 individual pathogenicity predictors into a single score for missense variants.

What It Does

• Ensemble score from 13 tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, phastCons
• Score 0-1: higher = more likely pathogenic
• Calibrated for rare variants (MAF <0.5%)
• Thresholds per Pejaver 2022: ≥0.773 = PP3_Moderate, ≥0.932 = PP3_Strong

How to Use

Web

• https://sites.google.com/site/revelgenomics/
• Download pre-computed scores (by chromosome)

Via dbNSFP (Recommended)

# Download dbNSFP (includes REVEL + 30 other predictors)
# Then query:
tabix dbNSFP4.5a_variant.chr15.gz 43600551-43600551

Via Ensembl VEP

# VEP includes REVEL plugin
vep --input_file variants.vcf --plugin REVEL,revel_scores.tsv.gz

Via VarSome / Franklin

Both web tools show REVEL score on their variant pages.

Verified Status

VERIFIED — STRC E1659A REVEL score: 0.789. Exceeds PP3_Moderate threshold (≥0.773) per Pejaver 2022 calibration. This was a critical correction — previous analysis incorrectly cited 0.65.

STRC Research Usage

• STRC E1659A Conservation and Reclassification — PP3 evidence (0.789 ≥ 0.773 = Moderate)
• STRC Variant c.4976A>C — Misha — ACMG classification
• Confirmed: score below PP3_Strong threshold (0.932), so only Moderate

Critical Notes

• REVEL 0.789 ≠ PP3_Strong — only reaches Moderate per Pejaver 2022
• Complements AlphaMissense — different methodology, similar conclusion
• Pejaver 2022 thresholds are ClinGen-recommended — use these, not arbitrary cutoffs

Connections

• AlphaMissense [see-also] — DeepMind predictor (complementary)
• CADD [see-also] — another ensemble method
• STRC E1659A Conservation and Reclassification [used-in]
• InterVar [see-also] — automated ACMG with REVEL
• VarSome [see-also] — shows REVEL on variant pages