Is HPS3 p.Asp886= (c.2658C>T) pathogenic?

HPS3 p.Asp886= (c.2658C>T) is classified Conflicting classifications of pathogenicity in HPS3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-26). Very rare (popmax 0.00017%, nfe); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Asp886= (c.2658C>T)?

HPS3 p.Asp886= (c.2658C>T) is associated with Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Asp886= (c.2658C>T) in the general population?

HPS3 p.Asp886= (c.2658C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

HPS3 p.Asp886=

c.2658C>T · rs141916243 · VCV343712

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Hermansky-Pudlak syndrome 3

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 0.26	GERP -0.84, phastCons 0.98
Overall
CADD	7.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,790 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,578 alleles · very rare

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.Asp886=
Coding: c.2658C>T
MANE Select: NM_000096 · reported on NM_032383
dbSNP: rs141916243
Type: single nucleotide variant
Location: chr3:149167102 (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-asp886 (accessed [today's date]).

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