HAP1 p.Ala21=
c.63A>G · rs1555592335 · VCV3043171
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0172%, mid)
Conditions
1
HAP1-related disorder
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 -0.6 | GERP -2.8 |
| Overall | ||
| CADD | 4.813 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0172%
Middle Eastern · 1/5,814 alleles
Filtering AF
0.00433%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00298%
Overall
0.000501%
8/1,597,168 alleles · ultra-rare
exomes 7/1,445,062 · genomes 1/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0172% | 5,814 |
| Admixed American | 0.0101% | 9,864 |
| European (non-Finnish) | 8.53e-05% | 1,172,556 |
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.Ala21=
- Coding
- c.63A>G
- MANE Select
- NM_177977
- dbSNP
- rs1555592335
- Type
- single nucleotide variant
- Location
- chr17:41734572 (GRCh38)
- Gene constraint
- LOEUF 1.31 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.28
- Residue 21
- the 'disordered' region
Disease context
HAP1-related disorder
Similar variants
- HAP1 c.1201-4C>T Likely benign same condition
- HAP1 c.1201-7C>T Likely benign same condition
- HAP1 c.470-7C>G Likely benign same condition
- HAP1 p.Ala505Val Benign same condition
- HAP1 p.Arg116Trp Likely benign same condition
- HAP1 p.Asp339Asn Likely benign same condition
- HAP1 p.Leu408Phe Benign ⚠ same condition
- HAP1 p.Pro187His Likely benign same condition
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-ala21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown