Is HPS3 p.Val595= (c.1785A>G) pathogenic?

HPS3 p.Val595= (c.1785A>G) is classified Conflicting classifications of pathogenicity in HPS3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-19). Rare (popmax 0.412%, eas); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Val595= (c.1785A>G)?

HPS3 p.Val595= (c.1785A>G) is associated with Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Val595= (c.1785A>G) in the general population?

HPS3 p.Val595= (c.1785A>G) is rare (popmax 0.412%, eas) (gnomAD).

HPS3 p.Val595=

c.1785A>G · rs150262900 · VCV761877

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.412%, eas)

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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -3.5
Overall
CADD	1.311	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.412% East Asian · 185/44,876 alleles

Filtering AF 0.364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.345%

Overall 0.0115% 186/1,612,384 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.412%	243
Remaining individualsnot grpmax-eligible	0.0016%	62,420

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.Val595=
Coding: c.1785A>G
MANE Select: NM_032383
dbSNP: rs150262900
Type: single nucleotide variant
Location: chr3:149158759 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.67

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

Similar variants

HPS3 c.1163+1G>A Pathogenic ★★ same condition
HPS3 c.1246-2A>T Likely pathogenic ★★ same condition
HPS3 c.1509+1G>A Likely pathogenic ★★ same condition
HPS3 c.1873-1G>A Likely pathogenic ★★ same condition
HPS3 c.2106+1G>T Likely pathogenic ★★ same condition
HPS3 c.2292+1G>A Likely pathogenic ★★ same condition
HPS3 p.Arg107Ter Pathogenic ★★ same condition
HPS3 p.Arg231Ter Pathogenic/Likely pathogenic ★★ same condition

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-val595 (accessed [today's date]).

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