Is ASIC3 p.Ser25Pro (c.73T>C) pathogenic?

ASIC3 p.Ser25Pro (c.73T>C) is classified Uncertain significance in ASIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: ambiguous (0.5216); Ultra-rare (popmax 0.0225%, eas).

How common is ASIC3 p.Ser25Pro (c.73T>C) in the general population?

ASIC3 p.Ser25Pro (c.73T>C) is ultra-rare (popmax 0.0225%, eas) (gnomAD).

What do computational predictors say about ASIC3 p.Ser25Pro (c.73T>C)?

AlphaMissense predicts ambiguous (score 0.5216) — an in-silico prediction, not a clinical call.

ASIC3 p.Ser25Pro

c.73T>C · rs147990189 · VCV2537503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5216 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, eas)

Computational evidence

Protein change
AlphaMissense	0.5216	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -12.33	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.78, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,763 bp · p 0.2 · regional, not allelic
Overall
CADD	18.16	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

Grpmax group 0.0225% East Asian · 10/44,480 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00924%

Overall 0.000627% 10/1,595,854 alleles · ultra-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: ASIC3
Protein: p.Ser25Pro
Coding: c.73T>C
MANE Select: NM_004769
dbSNP: rs147990189
Type: single nucleotide variant
Location: chr7:151048958 (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.Ser25Ala Uncertain significance ★ ⚠ same residue
ASIC3 p.Ser25Leu Uncertain significance ★ ⚠ same residue
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

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-ser25pro (accessed [today's date]).

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