Is HPS3 p.Phe989= (c.2967T>C) pathogenic?

HPS3 p.Phe989= (c.2967T>C) is classified Likely benign in HPS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). Very rare (popmax 0.00195%, nfe); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Phe989= (c.2967T>C)?

HPS3 p.Phe989= (c.2967T>C) is associated with Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Phe989= (c.2967T>C) in the general population?

HPS3 p.Phe989= (c.2967T>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

HPS3 p.Phe989=

c.2967T>C · rs1170514296 · VCV1104343

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Conditions

Hermansky-Pudlak syndrome 3

⚠ 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 1.5	GERP -1.5, phastCons 1
Overall
CADD	9.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,624 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00155% 25/1,613,554 alleles · very rare exomes 24/1,461,340 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,288
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Phe989=
Coding: c.2967T>C
MANE Select: NM_032383
dbSNP: rs1170514296
Type: single nucleotide variant
Location: chr3:149172174 (GRCh38)

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

Disease context

Hermansky-Pudlak syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-phe989 (accessed [today's date]).

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