HAP1 p.Ala117Val
c.350C>T · VCV4674880
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2008 | likely benign |
|---|---|---|
| REVEL | 0.099 | moderately benign-leaning |
| SaProt | LLR -6.91 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 9,930 bp · p 0.16 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0257% | 3,885 |
| European (non-Finnish)grpmax | 0.0126% | 7,958 |
| African / African-American | 0.00534% | 18,717 |
| Finnishnot grpmax-eligible | 0.0048% | 20,823 |
| South Asian | 0.0011% | 90,610 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- HAP1
- Protein
- p.Ala117Val
- Coding
- c.350C>T
- MANE Select
- NM_177977
- Type
- single nucleotide variant
- Location
- chr17:41734285 (GRCh38)
- Gene constraint
- LOEUF 1.31 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.28
- Residue 117
- the hap1 n-terminal domain
Similar variants
- HAP1 p.Arg106Pro Uncertain significance ★★ ⚠ same type
- HAP1 p.Cys25Tyr Benign ★★ same type
- HAP1 p.Gly604Arg Benign ★★ same type
- HAP1 p.Ile496Val Benign ★★ same type
- HAP1 p.Leu348= Benign ★★ same type
- HAP1 p.Ser616Ter Benign ★★ same type
- HAP1 p.Thr441Met Benign ★★ same type
- HAP1 p.Thr66Ala Likely benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hap1-p-ala117val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown