HPD p.Ala277=
c.831G>A · rs372058146 · VCV871741
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.46 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.61 | loss · gain 0.04 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.36 | GERP 0.45, phastCons 0.99 |
| Overall | ||
| CADD | 19.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,896 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00155%
25/1,613,836 alleles · ultra-rare
exomes 18/1,461,656 · genomes 7/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,979 |
| African / African-American | 0.00667% | 14,984 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| European (non-Finnish) | 0.0011% | 90,759 |
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
- HPD
- Protein
- p.Ala277=
- Coding
- c.831G>A
- MANE Select
- NM_002150
- dbSNP
- rs372058146
- Type
- single nucleotide variant
- Location
- chr12:121846862 (GRCh38)
- Gene constraint
- LOEUF 0.845 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.00 · 4 PDB
- Residue 277
- a UniProt-annotated variant site (in tyrsn3; likely pathogenic); the voc 2 domain; an α-helix
Similar variants
- HPD p.Arg225Ter Pathogenic/Likely pathogenic ★★ same type
- HPD p.Gln205Ter Pathogenic/Likely pathogenic ★★ same type
- HPD p.Tyr160Cys Likely pathogenic ★★ same type
- HPD c.198+3G>A Uncertain significance ★★ same type
- HPD p.Ala230Thr Uncertain significance ★★ ⚠ same type
- HPD p.Arg111Trp Uncertain significance ★★ ⚠ same type
- HPD p.Arg119Gln Uncertain significance ★★ ⚠ same type
- HPD p.Arg279Cys 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/hpd-p-ala277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown