HPS3 p.Ala376=
c.1128A>G · rs1722738295 · VCV991440
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Hermansky-Pudlak syndrome
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 -4 |
| Overall | ||
| CADD | 0.373 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HPS3
- Protein
- p.Ala376=
- Coding
- c.1128A>G
- MANE Select
- NM_032383
- dbSNP
- rs1722738295
- Type
- single nucleotide variant
- Location
- chr3:149145511 (GRCh38)
- Gene constraint
- LOEUF 0.684 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.67
Disease context
Hermansky-Pudlak syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hermansky-Pudlak syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Worldwide)
Similar variants
- HPS3 c.1163+1G>A Pathogenic ★★ same condition
- HPS3 c.1691+1G>A Pathogenic ★★ same condition
- HPS3 p.Arg397Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- HPS3 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS3 p.Gln245Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS3 p.Gln368Ter Likely pathogenic ★★ same condition
- HPS3 p.Glu275Ter Likely pathogenic ★★ same condition
- HPS3 p.Glu621Ter Pathogenic/Likely pathogenic ★★ same condition
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-ala376 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown