Is HPS3 p.Ser824= (c.2472G>A) pathogenic?

HPS3 p.Ser824= (c.2472G>A) is classified Likely benign in HPS3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0245%, eas).

How common is HPS3 p.Ser824= (c.2472G>A) in the general population?

HPS3 p.Ser824= (c.2472G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

HPS3 p.Ser824=

c.2472G>A · rs201221505 · VCV1144799

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

⚠ 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
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 -0.14	GERP -4.1, phastCons 0.004
Overall
CADD	1.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,870 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00887% 143/1,612,968 alleles · ultra-rare exomes 130/1,460,758 · genomes 13/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,079
African / African-American	0.00934%	10,709
European (non-Finnish)	0.00924%	10,817
Remaining individualsnot grpmax-eligible	0.00801%	12,490
South Asian	0.00659%	15,176
Admixed American	0.005%	19,989
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Finnishnot grpmax-eligible	0.00156%	64,016

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.Ser824=
Coding: c.2472G>A
MANE Select: NM_032383
dbSNP: rs201221505
Type: single nucleotide variant
Location: chr3:149162869 (GRCh38)

Full HPS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ser824 (accessed [today's date]).

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