Is HPS3 p.Ala482Pro (c.1444G>C) pathogenic?

HPS3 p.Ala482Pro (c.1444G>C) is classified Uncertain significance in HPS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0982); Very rare (popmax 8.5e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with HPS3 p.Ala482Pro (c.1444G>C)?

HPS3 p.Ala482Pro (c.1444G>C) is associated with Inborn genetic diseases (ClinVar).

How common is HPS3 p.Ala482Pro (c.1444G>C) in the general population?

HPS3 p.Ala482Pro (c.1444G>C) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about HPS3 p.Ala482Pro (c.1444G>C)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

HPS3 p.Ala482Pro

c.1444G>C · rs1723366326 · VCV2158953

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1, phastCons 0.002
Regional constraint	o/e 0.99	unconstrained · MANE · 42 kb · p 0.79 · regional, not allelic
Overall
CADD	21.5	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 8.5e-05% European (non-Finnish) · 1/1,177,090 alleles

Overall 6.21e-05% 1/1,610,838 alleles · very rare exomes 1/1,458,560 · genomes 0/152,278 · joint denominator

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.Ala482Pro
Coding: c.1444G>C
MANE Select: NM_032383
dbSNP: rs1723366326
Type: single nucleotide variant
Location: chr3:149155150 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HPS3 p.Ala482= Likely benign ★ same residue
HPS3 p.Ala401Val Uncertain significance ★★ ⚠ same condition
HPS3 p.Arg66Cys Uncertain significance ★★ ⚠ same condition
HPS3 p.Arg89Cys Uncertain significance ★★ ⚠ same condition
HPS3 p.Arg89His Uncertain significance ★★ ⚠ same condition
HPS3 p.Cys254Arg Uncertain significance ★★ ⚠ same condition
HPS3 p.Cys425Tyr Uncertain significance ★★ ⚠ same condition
HPS3 p.Gln461Pro Uncertain significance ★★ ⚠ 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-ala482pro (accessed [today's date]).

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