Is ACTN2 p.Phe345fs (c.1034del) pathogenic?

ACTN2 p.Phe345fs (c.1034del) is classified Uncertain significance in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). No gnomAD frequency available for this variant; Associated with dilated cardiomyopathy 1AA.

What condition is associated with ACTN2 p.Phe345fs (c.1034del)?

ACTN2 p.Phe345fs (c.1034del) is associated with dilated cardiomyopathy 1AA (ClinVar).

How common is ACTN2 p.Phe345fs (c.1034del) in the general population?

ACTN2 p.Phe345fs (c.1034del) is no gnomAD frequency available for this variant (gnomAD).

ACTN2 p.Phe345fs

c.1034del · rs2527599747 · VCV2579647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dilated cardiomyopathy 1AA

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -0.69, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTN2
Protein: p.Phe345fs
Coding: c.1034del
MANE Select: NM_001103
dbSNP: rs2527599747
Type: Deletion
Location: chr1:236739458 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB
Residue 345: 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

Similar variants

ACTN2 c.242-2_242-1del Uncertain significance ★★ same condition
ACTN2 p.Glu853fs Uncertain significance ★★ same condition
ACTN2 p.Pro240fs Uncertain significance ★★ same condition
ACTN2 p.Leu554fs Likely pathogenic ★ same condition
ACTN2 c.1249_1255+1del Uncertain significance ★ same condition
ACTN2 c.1407-541_1446del Uncertain significance ★ same condition
ACTN2 c.1657-2del Uncertain significance ★ same condition
ACTN2 c.615+4_615+6del 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-phe345fs (accessed [today's date]).

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