Is ASIC2 p.Ala382Val (c.1145C>T) pathogenic?

ASIC2 p.Ala382Val (c.1145C>T) is classified Uncertain significance in ASIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.2898); Very rare (popmax 8.48e-05%, nfe).

How common is ASIC2 p.Ala382Val (c.1145C>T) in the general population?

ASIC2 p.Ala382Val (c.1145C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ASIC2 p.Ala382Val (c.1145C>T)?

AlphaMissense predicts likely benign (score 0.2898) — an in-silico prediction, not a clinical call.

ASIC2 p.Ala382Val

c.1145C>T · rs2508824562 · VCV3130352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2898	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -8.97	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 75 kb · p 0.00015 · regional, not allelic
Overall
CADD	26.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A331V vs ClinVar A382V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,774 alleles

Overall 6.84e-05% 1/1,461,326 alleles · very rare

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: ASIC2
Protein: p.Ala382Val
Coding: c.1145C>T
MANE Select: NM_183377
dbSNP: rs2508824562
Type: single nucleotide variant
Location: chr17:33025976 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 1 PDB
Residue 382: an α-helix

Full ASIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC2 c.988-4G>A Benign ★★ same type
ASIC2 p.Ala293= Benign ★★ same type
ASIC2 p.Ala129Thr Uncertain significance ★ ⚠ same type
ASIC2 p.Ala136Val Uncertain significance ★ ⚠ same type
ASIC2 p.Ala28Glu Uncertain significance ★ same type
ASIC2 p.Ala402Val Uncertain significance ★ ⚠ same type
ASIC2 p.Ala47Thr Uncertain significance ★ same type
ASIC2 p.Ala79Ser 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/asic2-p-ala382val (accessed [today's date]).

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