Is ACTN2 p.Ser813= (c.2439C>T) pathogenic?

ACTN2 p.Ser813= (c.2439C>T) is classified Likely benign in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-01). Very rare (popmax 0.0011%, sas); Associated with cardiomyopathy.

What condition is associated with ACTN2 p.Ser813= (c.2439C>T)?

ACTN2 p.Ser813= (c.2439C>T) is associated with cardiomyopathy (ClinVar).

How common is ACTN2 p.Ser813= (c.2439C>T) in the general population?

ACTN2 p.Ser813= (c.2439C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ACTN2 p.Ser813=

c.2439C>T · rs1659693123 · VCV915739

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

cardiomyopathy

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 1.1	GERP 0.52, phastCons 1
Overall
CADD	13.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 6.84e-05% 1/1,461,892 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
Protein: p.Ser813=
Coding: c.2439C>T
MANE Select: NM_001103
dbSNP: rs1659693123
Type: single nucleotide variant
Location: chr1:236761086 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB
Residue 813: an α-helix; the ef-hand 2 domain

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

Disease context

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

Similar variants

ACTN2 p.Ser813Thr Uncertain significance ★★ ⚠ same residue
ACTN2 c.1107+3G>A Uncertain significance ★★ same condition
ACTN2 c.127-3C>A Uncertain significance ★★ same condition
ACTN2 c.536+6C>G Uncertain significance ★★ same condition
ACTN2 c.*10T>C Uncertain significance ★★ same condition
ACTN2 p.Ala259Thr Uncertain significance ★★ ⚠ same condition
ACTN2 p.Ala265Val Uncertain significance ★★ ⚠ same condition
ACTN2 p.Arg194Gln 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-ser813 (accessed [today's date]).

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