Is HPS3 p.Tyr855= (c.2565T>C) pathogenic?

HPS3 p.Tyr855= (c.2565T>C) is classified Likely benign in HPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Ultra-rare (popmax 0.0108%, afr).

How common is HPS3 p.Tyr855= (c.2565T>C) in the general population?

HPS3 p.Tyr855= (c.2565T>C) is ultra-rare (popmax 0.0108%, afr) (gnomAD).

HPS3 p.Tyr855=

c.2565T>C · rs771573991 · VCV1100151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, afr)

⚠ 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 -2.5	GERP -4.4
Overall
CADD	1.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% African / African-American · 8/74,034 alleles

Filtering AF 0.00533% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00384%

Overall 0.000712% 11/1,544,380 alleles · ultra-rare exomes 6/1,392,132 · genomes 5/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0108%	9,254
Remaining individualsnot grpmax-eligible	0.00498%	20,069

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.Tyr855=
Coding: c.2565T>C
MANE Select: NM_032383
dbSNP: rs771573991
Type: single nucleotide variant
Location: chr3:149163925 (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-tyr855 (accessed [today's date]).

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