Is ASIC3 p.Arg42Pro (c.125G>C) pathogenic?

ASIC3 p.Arg42Pro (c.125G>C) is classified Uncertain significance in ASIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: ambiguous (0.5145); Absent from gnomAD v4.1.

How common is ASIC3 p.Arg42Pro (c.125G>C) in the general population?

ASIC3 p.Arg42Pro (c.125G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASIC3 p.Arg42Pro (c.125G>C)?

AlphaMissense predicts ambiguous (score 0.5145) — an in-silico prediction, not a clinical call.

ASIC3 p.Arg42Pro

c.125G>C · rs114837285 · VCV3130363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5145 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5145	ambiguous
REVEL	0.691	pathogenic-leaning
SaProt	LLR -16.94	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.84, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,763 bp · p 0.2 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASIC3
Protein: p.Arg42Pro
Coding: c.125G>C
MANE Select: NM_004769
dbSNP: rs114837285
Type: single nucleotide variant
Location: chr7:151049010 (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-arg42pro (accessed [today's date]).

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