HPS3 p.Ala482=
c.1446T>C · rs2473102740 · VCV2170167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00051%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -3.7 |
| Overall | ||
| CADD | 7.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00051%
European (non-Finnish) · 6/1,177,064 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000121%
Overall
0.000372%
6/1,610,880 alleles · very rare
exomes 6/1,458,528 · genomes 0/152,352 · joint denominator
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
- HPS3
- Protein
- p.Ala482=
- Coding
- c.1446T>C
- MANE Select
- NM_032383
- dbSNP
- rs2473102740
- Type
- single nucleotide variant
- Location
- chr3:149155152 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.67
Similar variants
- HPS3 p.Ala482Pro Uncertain significance ★★ ⚠ same residue
- HPS3 c.1163+1G>A Pathogenic ★★ same type
- HPS3 c.1246-2A>T Likely pathogenic ★★ same type
- HPS3 c.1509+1G>A Likely pathogenic ★★ same type
- HPS3 c.1691+1G>A Pathogenic ★★ same type
- HPS3 c.1692-2A>G Likely pathogenic ★★ same type
- HPS3 c.1873-1G>A Likely pathogenic ★★ same type
- HPS3 c.2106+1G>T Likely pathogenic ★★ 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/hps3-p-ala482 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown