Is HPS3 p.Arg900His (c.2699G>A) pathogenic?

HPS3 p.Arg900His (c.2699G>A) is classified Uncertain significance in HPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.00891%, eas); Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Arg900His (c.2699G>A)?

HPS3 p.Arg900His (c.2699G>A) is associated with Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Arg900His (c.2699G>A) in the general population?

HPS3 p.Arg900His (c.2699G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about HPS3 p.Arg900His (c.2699G>A)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

HPS3 p.Arg900His

c.2699G>A · rs202157837 · VCV343714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

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
AlphaMissense	0.1053	likely benign
REVEL	0.494	indeterminate
SaProt	LLR -7.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 42 kb · p 0.79 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000744% 12/1,613,850 alleles · very rare exomes 10/1,461,522 · genomes 2/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000593%	168,535

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.Arg900His
Coding: c.2699G>A
MANE Select: NM_032383
dbSNP: rs202157837
Type: single nucleotide variant
Location: chr3:149167143 (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-arg900his (accessed [today's date]).

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