Is ASIC1 p.His110Pro (c.329A>C) pathogenic?

ASIC1 p.His110Pro (c.329A>C) is classified Uncertain significance in ASIC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-25). AlphaMissense: likely pathogenic (0.9914); Very rare (popmax 8.47e-05%, nfe).

How common is ASIC1 p.His110Pro (c.329A>C) in the general population?

ASIC1 p.His110Pro (c.329A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ASIC1 p.His110Pro (c.329A>C)?

AlphaMissense predicts likely pathogenic (score 0.9914) — an in-silico prediction, not a clinical call.

ASIC1 p.His110Pro

c.329A>C · rs2539428792 · VCV2297646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9914	likely pathogenic · top 10% in ASIC1
REVEL	0.663	pathogenic-leaning
SaProt	LLR -16.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 20 kb · p 8.7e-10 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.84e-05% 1/1,461,778 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: ASIC1
Protein: p.His110Pro
Coding: c.329A>C
MANE Select: NM_001095
dbSNP: rs2539428792
Type: single nucleotide variant
Location: chr12:50059095 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 16 PDB
Residue 110: a disulfide bond; an α-helix

Full ASIC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC1 c.1206-9C>T Benign ★★ same type
ASIC1 c.1297+37A>G Benign ★★ same type
ASIC1 c.558+3G>A Benign ★★ same type
ASIC1 p.Ile224= Benign ★★ same type
ASIC1 p.Thr26= Benign ★★ same type
ASIC1 c.1297+33T>C Uncertain significance ★ same type
ASIC1 c.1297+45G>A Uncertain significance ★ same type
ASIC1 c.1297+48G>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/asic1-p-his110pro (accessed [today's date]).

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