Is ACTN2 p.Gln349= (c.1047G>A) pathogenic?

ACTN2 p.Gln349= (c.1047G>A) is classified Likely benign in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1AA.

What condition is associated with ACTN2 p.Gln349= (c.1047G>A)?

ACTN2 p.Gln349= (c.1047G>A) is associated with dilated cardiomyopathy 1AA, familial hypertrophic cardiomyopathy (ClinVar).

How common is ACTN2 p.Gln349= (c.1047G>A) in the general population?

ACTN2 p.Gln349= (c.1047G>A) is absent from gnomAD v4.1 (gnomAD).

ACTN2 p.Gln349=

c.1047G>A · rs2527599801 · VCV1896106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dilated cardiomyopathy 1AA

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 7.6	GERP 1.2, phastCons 1
Overall
CADD	10.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTN2
Protein: p.Gln349=
Coding: c.1047G>A
MANE Select: NM_001103
dbSNP: rs2527599801
Type: single nucleotide variant
Location: chr1:236739472 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB
Residue 349: an α-helix

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

Disease context

dilated cardiomyopathy 1AA — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypertrophic cardiomyopathy

Similar variants

ACTN2 p.Gln349Arg Uncertain significance ★ ⚠ same residue
ACTN2 p.Gln349Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-gln349 (accessed [today's date]).

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