Is HPS3 p.Pro916= (c.2748G>A) pathogenic?

HPS3 p.Pro916= (c.2748G>A) is classified Likely benign in HPS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Very rare (popmax 0.004%, afr).

How common is HPS3 p.Pro916= (c.2748G>A) in the general population?

HPS3 p.Pro916= (c.2748G>A) is very rare (popmax 0.004%, afr) (gnomAD).

HPS3 p.Pro916=

c.2748G>A · rs1333599936 · VCV1118584

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -7	GERP -4.2
Overall
CADD	1.295	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,613,696 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0011%	91,076
European (non-Finnish)	0.000339%	294,957

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.Pro916=
Coding: c.2748G>A
MANE Select: NM_032383
dbSNP: rs1333599936
Type: single nucleotide variant
Location: chr3:149167192 (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-pro916 (accessed [today's date]).

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