Is CTNNA3 p.Ser2= (c.6A>T) pathogenic?

CTNNA3 p.Ser2= (c.6A>T) is classified Likely benign in CTNNA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). Very rare (popmax 0.0022%, sas); Associated with arrhythmogenic right ventricular dysplasia 13.

What condition is associated with CTNNA3 p.Ser2= (c.6A>T)?

CTNNA3 p.Ser2= (c.6A>T) is associated with arrhythmogenic right ventricular dysplasia 13 (ClinVar).

How common is CTNNA3 p.Ser2= (c.6A>T) in the general population?

CTNNA3 p.Ser2= (c.6A>T) is very rare (popmax 0.0022%, sas) (gnomAD).

CTNNA3 p.Ser2=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.6A>T · rs779894670 · VCV1756593

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -2.8	GERP -4
Overall
CADD	0.496	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,998 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,612,916 alleles · very rare exomes 12/1,460,648 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,499
European (non-Finnish)	0.000848%	117,917

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.Ser2=
Coding: c.6A>T
MANE Select: NM_013266
dbSNP: rs779894670
Type: single nucleotide variant
Location: chr10:67647508 (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

CTNNA3 p.Ser2Ter 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-ser2 (accessed [today's date]).

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