HAP1 p.Leu348=
c.1044C>T · rs116828637 · VCV788808
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 5.957 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.02%
African / African-American · 3,015/74,978 alleles
Filtering AF
3.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.85%
Overall
0.239%
3,858/1,612,254 alleles · low-frequency
exomes 1,964/1,459,968 · genomes 1,894/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.02% | 25 |
| Middle Eastern | 0.66% | 151 |
| Admixed American | 0.538% | 186 |
| Remaining individualsnot grpmax-eligible | 0.314% | 319 |
| European (non-Finnish) | 0.0224% | 4,463 |
| South Asian | 0.0198% | 5,058 |
| Finnishnot grpmax-eligible | 0.00312% | 32,021 |
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.Leu348=
- Coding
- c.1044C>T
- MANE Select
- NM_177977
- dbSNP
- rs116828637
- Type
- single nucleotide variant
- Location
- chr17:41731518 (GRCh38)
- Gene constraint
- LOEUF 1.31 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.28
- Residue 348
- 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.Ser616Ter Benign ★★ same type
- HAP1 p.Thr441Met Benign ★★ same type
- HAP1 p.Thr66Ala Likely benign ★★ same type
- HAP1 p.Val369Ala 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-leu348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown