Is HPS3 p.Val843Ile (c.2527G>A) pathogenic?

HPS3 p.Val843Ile (c.2527G>A) is classified Benign in HPS3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.068); Low-frequency (popmax 1.03%, sas); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Val843Ile (c.2527G>A)?

HPS3 p.Val843Ile (c.2527G>A) is associated with Hermansky-Pudlak syndrome 3, Hermansky-Pudlak syndrome (ClinVar).

How common is HPS3 p.Val843Ile (c.2527G>A) in the general population?

HPS3 p.Val843Ile (c.2527G>A) is low-frequency (popmax 1.03%, sas) (gnomAD).

What do computational predictors say about HPS3 p.Val843Ile (c.2527G>A)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

HPS3 p.Val843Ile

c.2527G>A · rs150765088 · VCV756752

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hermansky-Pudlak syndrome 3

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.008	GERP -4.4
Regional constraint	o/e 0.99	unconstrained · MANE · 42 kb · p 0.79 · regional, not allelic
Overall
CADD	1.653	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% South Asian · 928/90,418 alleles

Filtering AF 0.972% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.95%

Overall 0.0622% 986/1,586,202 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.03%	97
Remaining individualsnot grpmax-eligible	0.0715%	1,399
Middle Eastern	0.0168%	5,954
African / African-American	0.00803%	12,457
East Asian	0.00224%	44,608
European (non-Finnish)	0.00052%	192,451

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.Val843Ile
Coding: c.2527G>A
MANE Select: NM_000096 · reported on NM_032383
dbSNP: rs150765088
Type: single nucleotide variant
Location: chr3:149163887 (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-val843ile (accessed [today's date]).

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