Is ASIC3 p.Phe233Ser (c.698T>C) pathogenic?

ASIC3 p.Phe233Ser (c.698T>C) is classified Uncertain significance in ASIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely benign (0.3296); Very rare (popmax 8.48e-05%, nfe).

How common is ASIC3 p.Phe233Ser (c.698T>C) in the general population?

ASIC3 p.Phe233Ser (c.698T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ASIC3 p.Phe233Ser (c.698T>C)?

AlphaMissense predicts likely benign (score 0.3296) — an in-silico prediction, not a clinical call.

ASIC3 p.Phe233Ser

c.698T>C · rs1796741193 · VCV3130373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3296 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3296	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.18, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 3,763 bp · p 0.2 · regional, not allelic
Overall
CADD	23.1	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 8.48e-05% European (non-Finnish) · 1/1,179,898 alleles

Overall 6.84e-05% 1/1,461,652 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: ASIC3
Protein: p.Phe233Ser
Coding: c.698T>C
MANE Select: NM_004769
dbSNP: rs1796741193
Type: single nucleotide variant
Location: chr7:151050493 (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-phe233ser (accessed [today's date]).

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