Is ASIC3 p.Val32Ile (c.94G>A) pathogenic?

ASIC3 p.Val32Ile (c.94G>A) is classified Uncertain significance in ASIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely benign (0.0731); Ultra-rare (popmax 0.0134%, amr).

How common is ASIC3 p.Val32Ile (c.94G>A) in the general population?

ASIC3 p.Val32Ile (c.94G>A) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about ASIC3 p.Val32Ile (c.94G>A)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

ASIC3 p.Val32Ile

c.94G>A · rs146916223 · VCV3130376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -7.63	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 0.22	GERP -3.8, phastCons 0.002
Regional constraint	o/e 1.05	unconstrained · MANE · 3,763 bp · p 0.2 · regional, not allelic
Overall
CADD	0.102	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 0.0134% Admixed American · 8/59,818 alleles

Filtering AF 0.00663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00484%

Overall 0.00292% 47/1,607,706 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,477
South Asian	0.0055%	18,178
East Asian	0.00447%	22,357
Remaining individualsnot grpmax-eligible	0.00322%	31,089
European (non-Finnish)	0.00255%	39,187

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: ASIC3
Protein: p.Val32Ile
Coding: c.94G>A
MANE Select: NM_004769
dbSNP: rs146916223
Type: single nucleotide variant
Location: chr7:151048979 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.15

Full ASIC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC3 p.Arg79Ter Uncertain significance ★★ same type
ASIC3 p.Pro289Ser Benign ★★ same type
ASIC3 c.1518-4G>A Uncertain significance ★ same type
ASIC3 c.*27C>T Uncertain significance ★ same type
ASIC3 c.*3C>A Uncertain significance ★ same type
ASIC3 c.*3C>T Uncertain significance ★ same type
ASIC3 p.Ala110Ser Uncertain significance ★ ⚠ same type
ASIC3 p.Ala120Thr Uncertain significance ★ ⚠ same type

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/asic3-p-val32ile (accessed [today's date]).

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