Is ACTN2 p.Lys71Ter (c.210dup) pathogenic?

ACTN2 p.Lys71Ter (c.210dup) is classified Pathogenic in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-20). Associated with left ventricular noncompaction.

What condition is associated with ACTN2 p.Lys71Ter (c.210dup)?

ACTN2 p.Lys71Ter (c.210dup) is associated with left ventricular noncompaction (ClinVar).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACTN2 p.Lys71Ter

c.210dup · VCV4075274

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

Conditions

left ventricular noncompaction

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1

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

Variant & gene context

Gene: ACTN2
Protein: p.Lys71Ter
Coding: c.210dup
MANE Select: NM_001103
Type: Duplication
Location: chr1:236717939 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB
Residue 71: the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region

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

Disease context

left ventricular noncompaction — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

ACTN2 c.1255+2dup Uncertain significance ★ same type
ACTN2 c.126+20_126+43dup Uncertain significance ★ same type
ACTN2 p.Arg767fs Uncertain significance ★ same type
ACTN2 p.Asp17fs Uncertain significance ★ same type
ACTN2 p.Asp29_Leu30insArgAsp Uncertain significance ★ same type
ACTN2 p.Gly384_Lys405dup Uncertain significance ★ same type
ACTN2 p.Ile117fs Uncertain significance ★ same type
ACTN2 p.Lys679fs Uncertain significance ★ same type

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-lys71ter (accessed [today's date]).

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