Is ACTC1 p.Ala233= (c.699C>T) pathogenic?

ACTC1 p.Ala233= (c.699C>T) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Ala233= (c.699C>T)?

ACTC1 p.Ala233= (c.699C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 11 (ClinVar).

How common is ACTC1 p.Ala233= (c.699C>T) in the general population?

ACTC1 p.Ala233= (c.699C>T) is absent from gnomAD v4.1 (gnomAD).

ACTC1 p.Ala233=

c.699C>T · rs1595760786 · VCV1569142

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 -0.11	GERP -4.7, phastCons 0.051
Overall
CADD	8.621	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTC1
Protein: p.Ala233=
Coding: c.699C>T
MANE Select: NM_005159
dbSNP: rs1595760786
Type: single nucleotide variant
Location: chr15:34792199 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 233: an α-helix

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: hypertrophic cardiomyopathy hypertrophic cardiomyopathy 11 atrial septal defect 5 dilated cardiomyopathy 1R

Similar variants

ACTC1 p.Ala233Pro Uncertain significance ★ ⚠ same residue
ACTC1 p.Glu101Lys Pathogenic ★★★ same condition
ACTC1 p.Gly345Val Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Pro266Leu Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Ala297Ser Pathogenic ★★ ⚠ same condition
ACTC1 p.Gly247Asp Pathogenic/Likely pathogenic ★★ same condition
ACTC1 p.Thr128Ile Likely pathogenic ★★ 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/actc1-p-ala233 (accessed [today's date]).

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