Is HPS3 p.Trp936Ter (c.2808G>A) pathogenic?

HPS3 p.Trp936Ter (c.2808G>A) is classified Likely pathogenic in HPS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-18). Very rare (popmax 0.00224%, eas); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Trp936Ter (c.2808G>A)?

HPS3 p.Trp936Ter (c.2808G>A) is associated with Hermansky-Pudlak syndrome 3, Hermansky-Pudlak syndrome (ClinVar).

How common is HPS3 p.Trp936Ter (c.2808G>A) in the general population?

HPS3 p.Trp936Ter (c.2808G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

HPS3 p.Trp936Ter

c.2808G>A · rs760255783 · VCV2676079

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

Hermansky-Pudlak syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,742 alleles

Overall 6.91e-05% 1/1,446,660 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.Trp936Ter
Coding: c.2808G>A
MANE Select: NM_000096 · reported on NM_032383
dbSNP: rs760255783
Type: single nucleotide variant
Location: chr3:149167904 (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

Also linked: Hermansky-Pudlak syndrome

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-trp936ter (accessed [today's date]).

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