Is ACTC1 p.Glu239= (c.717G>A) pathogenic?

ACTC1 p.Glu239= (c.717G>A) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Very rare (popmax 0.00801%, afr); Associated with hypertrophic cardiomyopathy 11.

What condition is associated with ACTC1 p.Glu239= (c.717G>A)?

ACTC1 p.Glu239= (c.717G>A) is associated with hypertrophic cardiomyopathy 11, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is ACTC1 p.Glu239= (c.717G>A) in the general population?

ACTC1 p.Glu239= (c.717G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

ACTC1 p.Glu239=

c.717G>A · rs369019849 · VCV629731

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

hypertrophic cardiomyopathy 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
Overall
CADD	11.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,950 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00595% 96/1,614,126 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,492
European (non-Finnish)	0.00729%	13,721
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00156%	64,044

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: ACTC1
Protein: p.Glu239=
Coding: c.717G>A
dbSNP: rs369019849
Type: single nucleotide variant
Location: chr15:34792181 (GRCh38)

Full ACTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertrophic cardiomyopathy 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy atrial septal defect 5 dilated cardiomyopathy 1R

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/actc1-p-glu239 (accessed [today's date]).

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