HPCA p.Ala65=
c.195C>T · rs190500642 · VCV1980515
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0813%, 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 -14 | GERP -5.2 |
| Overall | ||
| CADD | 4.102 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0813%
African / African-American · 61/75,056 alleles
Filtering AF
0.0649%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.059%
Overall
0.00886%
143/1,614,232 alleles · ultra-rare
exomes 109/1,461,888 · genomes 34/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0813% | 1,230 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Admixed American | 0.00666% | 15,008 |
| European (non-Finnish) | 0.00449% | 22,265 |
| East Asian | 0.00223% | 44,890 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
| South Asian | 0.0011% | 91,080 |
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
- HPCA
- Protein
- p.Ala65=
- Coding
- c.195C>T
- MANE Select
- NM_002143
- dbSNP
- rs190500642
- Type
- single nucleotide variant
- Location
- chr1:32889093 (GRCh38)
- Gene constraint
- LOEUF 0.557 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 4 PDB
- Residue 65
- the ef-hand 2 domain; an α-helix
Similar variants
- HPCA p.Lys147Met Uncertain significance ★★ same type
- HPCA c.484+32G>C Likely benign ★★ same type
- HPCA c.379-3C>T Uncertain significance ★ same type
- HPCA c.-5C>T Uncertain significance ★ same type
- HPCA p.Ala127Thr Uncertain significance ★ ⚠ same type
- HPCA p.Ala88Glu Uncertain significance ★ ⚠ same type
- HPCA p.Arg118Gln Uncertain significance ★ ⚠ same type
- HPCA p.Arg17Gln Uncertain significance ★ ⚠ 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/hpca-p-ala65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown