Is HPS3 p.Ala889= (c.2667C>T) pathogenic?

HPS3 p.Ala889= (c.2667C>T) is classified Likely benign in HPS3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-19). Ultra-rare (popmax 0.0329%, mid); Associated with Hermansky-Pudlak syndrome.

What condition is associated with HPS3 p.Ala889= (c.2667C>T)?

HPS3 p.Ala889= (c.2667C>T) is associated with Hermansky-Pudlak syndrome (ClinVar).

How common is HPS3 p.Ala889= (c.2667C>T) in the general population?

HPS3 p.Ala889= (c.2667C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Hermansky-Pudlak syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HPS3 p.Ala889=

c.2667C>T · rs761310586 · VCV754425

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Hermansky-Pudlak syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.4	GERP -3.9
Overall
CADD	6.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00297% 48/1,613,690 alleles · ultra-rare exomes 45/1,461,490 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
East Asian	0.00446%	22,445
European (non-Finnish)	0.00331%	30,249
Remaining individualsnot grpmax-eligible	0.0032%	31,231
South Asian	0.0022%	45,536
Admixed American	0.00167%	59,996

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.Ala889=
Coding: c.2667C>T
MANE Select: NM_032383
dbSNP: rs761310586
Type: single nucleotide variant
Location: chr3:149167111 (GRCh38)

Full HPS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hermansky-Pudlak syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

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-ala889 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown