Is CTNNA3 p.Lys686= (c.2058G>A) pathogenic?

CTNNA3 p.Lys686= (c.2058G>A) is classified Likely benign in CTNNA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). Very rare (popmax 0.00334%, amr); Associated with arrhythmogenic right ventricular dysplasia 13.

What condition is associated with CTNNA3 p.Lys686= (c.2058G>A)?

CTNNA3 p.Lys686= (c.2058G>A) is associated with arrhythmogenic right ventricular dysplasia 13 (ClinVar).

How common is CTNNA3 p.Lys686= (c.2058G>A) in the general population?

CTNNA3 p.Lys686= (c.2058G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

CTNNA3 p.Lys686=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2058G>A · rs745562600 · VCV1603995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

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 -2.1	GERP -0.58
Overall
CADD	2.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,968 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,554 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,984
European (non-Finnish)	0.000254%	393,247

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.Lys686=
Coding: c.2058G>A
MANE Select: NM_013266
dbSNP: rs745562600
Type: single nucleotide variant
Location: chr10:66069409 (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 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
CTNNA3 p.Ala224Pro 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-lys686 (accessed [today's date]).

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