HPS3 p.Ala135=
c.405C>A · rs529624415 · VCV1976215
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -2.1 | GERP -1.8 |
| Overall | ||
| CADD | 5.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00031%
5/1,614,108 alleles · ultra-rare
exomes 5/1,461,836 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| European (non-Finnish) | 0.000254% | 393,328 |
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.Ala135=
- Coding
- c.405C>A
- MANE Select
- NM_032383
- dbSNP
- rs529624415
- Type
- single nucleotide variant
- Location
- chr3:149140191 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.67
Similar variants
- HPS3 p.Ala135Gly Uncertain significance ★★ ⚠ same residue
- HPS3 p.Ala135Ser Uncertain significance ★ ⚠ same residue
- HPS3 p.Ala135fs Pathogenic/Likely pathogenic ★★ 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
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-ala135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown