HAP1 p.Leu341Pro
c.1022T>C · VCV4033643
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4912 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4912 | ambiguous |
|---|---|---|
| REVEL | 0.164 | moderately benign-leaning |
| SaProt | LLR -11.93 | damaging |
| ⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.4 | GERP 0.15, phastCons 0.81 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 9,930 bp · p 0.16 · regional, not allelic |
| Overall | ||
| CADD | 23.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HAP1
- Protein
- p.Leu341Pro
- Coding
- c.1022T>C
- MANE Select
- NM_177977
- Type
- single nucleotide variant
- Location
- chr17:41731540 (GRCh38)
- Gene constraint
- LOEUF 1.31 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.28
- Residue 341
- 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-leu341pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown