Is CTNNA3 p.Val394= (c.1182C>T) pathogenic?

CTNNA3 p.Val394= (c.1182C>T) is classified Likely benign in CTNNA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-11). Very rare (popmax 0.00102%, nfe); Associated with arrhythmogenic right ventricular dysplasia 13.

What condition is associated with CTNNA3 p.Val394= (c.1182C>T)?

CTNNA3 p.Val394= (c.1182C>T) is associated with arrhythmogenic right ventricular dysplasia 13 (ClinVar).

How common is CTNNA3 p.Val394= (c.1182C>T) in the general population?

CTNNA3 p.Val394= (c.1182C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

CTNNA3 p.Val394=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1182C>T · rs927559123 · VCV1078930

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

arrhythmogenic right ventricular dysplasia 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -2.6, phastCons 0.69
Overall
CADD	4.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,644 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,380 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: CTNNA3
Protein: p.Val394=
Coding: c.1182C>T
MANE Select: NM_013266
dbSNP: rs927559123
Type: single nucleotide variant
Location: chr10:66766363 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 81.65

Full CTNNA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

LRRTM3 p.Pro394Leu Uncertain significance ★ ⚠ same residue
CTNNA3 c.100-7A>G Uncertain significance ★★ same condition
CTNNA3 c.843+1G>T Uncertain significance ★★ same condition
CTNNA3 p.Ala124Thr Uncertain significance ★★ ⚠ same condition
CTNNA3 p.Ala130Pro Uncertain significance ★★ ⚠ same condition
CTNNA3 p.Ala131Val Uncertain significance ★★ ⚠ same condition
CTNNA3 p.Ala165Thr Uncertain significance ★★ ⚠ same condition
CTNNA3 p.Ala188Val Uncertain significance ★★ ⚠ same condition

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/ctnna3-p-val394 (accessed [today's date]).

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