HPCA p.Asp60=
c.180C>T · rs555055449 · VCV779034
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
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 -6.7 | GERP -5.2 |
| Overall | ||
| CADD | 10.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,890 alleles
Filtering AF
0.00883%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00254%
41/1,614,232 alleles · ultra-rare
exomes 33/1,461,878 · genomes 8/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,611 |
| South Asian | 0.00549% | 18,217 |
| Admixed American | 0.00333% | 30,015 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| European (non-Finnish) | 0.00203% | 49,168 |
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.Asp60=
- Coding
- c.180C>T
- MANE Select
- NM_002143
- dbSNP
- rs555055449
- Type
- single nucleotide variant
- Location
- chr1:32889078 (GRCh38)
- Gene constraint
- LOEUF 0.557 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 4 PDB
- Residue 60
- 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-asp60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown