Is ACTN2 c.*979C>A pathogenic?

ACTN2 c.979C>A is classified Uncertain significance in ACTN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-21). Rare (popmax 0.339%, afr); Associated with dilated cardiomyopathy 1AA.

How common is ACTN2 c.*979C>A in the general population?

ACTN2 c.*979C>A is rare (popmax 0.339%, afr) (gnomAD).

ACTN2 c.*979C>A

Q: What condition is associated with ACTN2 c.*979C>A?

ACTN2 c.*979C>A is associated with dilated cardiomyopathy 1AA, myopathy, congenital, with structured cores and z-line abnormalities, myopathy, distal, 6, adult-onset, autosomal dominant (ClinVar).

rs181615071 · VCV874533

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.339%, afr)

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 -0.82	GERP -1.8
Non-coding constraint	Z 0.73	1 kb window · o/e 0.93 · regional · uncalibrated
Overall
CADD	4.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.339% African / African-American · 141/41,554 alleles

Filtering AF 0.294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.276%

Overall 0.0946% 144/152,288 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.339%	295
Admixed American	0.0196%	5,098

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
Coding: c.*979C>A
MANE Select: NM_001103
dbSNP: rs181615071
Type: single nucleotide variant
Location: chr1:236763598 (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

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

Also linked: myopathy, congenital, with structured cores and z-line abnormalities myopathy, distal, 6, adult-onset, autosomal dominant

Similar variants

ACTN2 p.Ala119Thr Pathogenic/Likely pathogenic ★★ same condition
ACTN2 p.Leu727Arg 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-c-star-979c-a (accessed [today's date]).

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