Is ACTC1 p.Pro309= (c.927T>C) pathogenic?

ACTC1 p.Pro309= (c.927T>C) is classified Benign/Likely benign in ACTC1 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-04). Common (popmax 7.45%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Pro309= (c.927T>C)?

ACTC1 p.Pro309= (c.927T>C) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

ACTC1 p.Pro309=

Q: How common is ACTC1 p.Pro309= (c.927T>C) in the general population?

ACTC1 p.Pro309= (c.927T>C) is common (popmax 7.45%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.927T>C · rs2307493 · VCV45194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Common

common (popmax 7.45%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 0.31	GERP -1.1, phastCons 0.49
Overall
CADD	10.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.45% African / African-American · 5,586/75,008 alleles

Filtering AF 7.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.22%

Overall 0.736% 11,872/1,613,710 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.45%	13
Middle Eastern	1.58%	63
Admixed American	0.908%	110
Remaining individualsnot grpmax-eligible	0.885%	113
European (non-Finnish)	0.418%	239
South Asian	0.128%	778
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,114
East Asian	0.0379%	2,639
Finnishnot grpmax-eligible	0.0234%	4,268

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.Pro309=
Coding: c.927T>C
dbSNP: rs2307493
Type: single nucleotide variant
Location: chr15:34791177 (GRCh38)

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

Disease context

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

Also linked: cardiomyopathy hypertrophic cardiomyopathy hypertrophic cardiomyopathy 11 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-pro309 (accessed [today's date]).

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