Is ACTN2 p.Thr713= (c.2139G>A) pathogenic?

ACTN2 p.Thr713= (c.2139G>A) is classified Benign/Likely benign in ACTN2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ACTN2 p.Thr713= (c.2139G>A)?

ACTN2 p.Thr713= (c.2139G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1AA (ClinVar).

ACTN2 p.Thr713=

Q: How common is ACTN2 p.Thr713= (c.2139G>A) in the general population?

ACTN2 p.Thr713= (c.2139G>A) is common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2139G>A · rs34975493 · VCV35649

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 -8.3	GERP -4.5
Overall
CADD	0.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.5% African / African-American · 8,647/74,994 alleles

Filtering AF 11.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.2%

Overall 0.601% 9,697/1,614,082 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.5%	9
Remaining individualsnot grpmax-eligible	0.702%	142
Admixed American	0.673%	149
Middle Eastern	0.314%	319
South Asian	0.0253%	3,960
European (non-Finnish)	0.014%	7,152

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: ACTN2
Protein: p.Thr713=
Coding: c.2139G>A
MANE Select: NM_001103
dbSNP: rs34975493
Type: single nucleotide variant
Location: chr1:236755183 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB

Full ACTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy 1AA familial hypertrophic cardiomyopathy

Similar variants

ACTN2 p.Thr713Met Uncertain significance ★★ ⚠ same residue
ACTN2 p.Ala119Thr Pathogenic/Likely pathogenic ★★ same condition
ACTN2 p.Thr247Met Likely pathogenic ★★ same condition
ACTN2 c.1107+3G>A Uncertain significance ★★ same condition
ACTN2 c.1108-10A>G Uncertain significance ★★ same condition
ACTN2 c.1255+1G>C Uncertain significance ★★ same condition
ACTN2 c.126+2T>G Uncertain significance ★★ same condition
ACTN2 c.127-3C>A 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/actn2-p-thr713 (accessed [today's date]).

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