Is ACTN2 c.1839+15del pathogenic?

ACTN2 c.1839+15del is classified Likely benign in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-02). Very rare (popmax 8.48e-05%, nfe); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ACTN2 c.1839+15del?

ACTN2 c.1839+15del is associated with familial hypertrophic cardiomyopathy, dilated cardiomyopathy 1AA (ClinVar).

How common is ACTN2 c.1839+15del in the general population?

ACTN2 c.1839+15del is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ACTN2 c.1839+15del

rs2527636885 · VCV2935538

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +15	near-intronic (+15 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.9	GERP -3.6

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,798 alleles

Overall 6.84e-05% 1/1,461,548 alleles · very rare

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.1839+15del
MANE Select: NM_001103
dbSNP: rs2527636885
Type: Deletion
Location: chr1:236751665 (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

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

Also linked: dilated cardiomyopathy 1AA

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-c-1839-plus-15del (accessed [today's date]).

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