Is ACTN2 p.Asp17fs (c.49dup) pathogenic?

ACTN2 p.Asp17fs (c.49dup) is classified Uncertain significance in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). Absent from gnomAD; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ACTN2 p.Asp17fs (c.49dup)?

ACTN2 p.Asp17fs (c.49dup) is associated with familial hypertrophic cardiomyopathy, dilated cardiomyopathy 1AA (ClinVar).

How common is ACTN2 p.Asp17fs (c.49dup) in the general population?

ACTN2 p.Asp17fs (c.49dup) is absent from gnomAD (gnomAD).

ACTN2 p.Asp17fs

c.49dup · rs1665883260 · VCV2948185

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

familial hypertrophic cardiomyopathy

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 1 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP -0.75, 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.Asp17fs
Coding: c.49dup
MANE Select: NM_001103
dbSNP: rs1665883260
Type: Duplication
Location: chr1:236686720 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB
Residue 17: the 'actin-binding' region

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

Disease context

familial hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1AA

Similar variants

ACTN2 c.126+20_126+43dup Uncertain significance ★ same condition
ACTN2 p.Asp17Asn Uncertain significance ★ same residue
ACTN2 p.Asp29_Leu30insArgAsp Uncertain significance ★ same condition
ACTN2 p.Gly384_Lys405dup Uncertain significance ★ same condition
ACTN2 p.Lys679fs Uncertain significance ★ same condition
ACTN2 p.Met773fs Uncertain significance ★ same condition
ACTN2 p.Ser624fs Uncertain significance ★ same condition
ACTN2 c.126+11dup Benign ★ 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-asp17fs (accessed [today's date]).

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