Is ACTC1 p.Ile153= (c.459T>C) pathogenic?

ACTC1 p.Ile153= (c.459T>C) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-27). Very rare (popmax 0.00133%, afr); Associated with hypertrophic cardiomyopathy 11.

What condition is associated with ACTC1 p.Ile153= (c.459T>C)?

ACTC1 p.Ile153= (c.459T>C) is associated with hypertrophic cardiomyopathy 11, atrial septal defect 5, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Ile153= (c.459T>C) in the general population?

ACTC1 p.Ile153= (c.459T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

ACTC1 p.Ile153=

c.459T>C · rs2140431034 · VCV1151190

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.003, phastCons 0.075
Overall
CADD	3.867	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,042 alleles

Overall 6.2e-05% 1/1,614,142 alleles · very rare exomes 1/1,461,884 · genomes 0/152,258 · joint denominator

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.Ile153=
Coding: c.459T>C
MANE Select: NM_005159
dbSNP: rs2140431034
Type: single nucleotide variant
Location: chr15:34792565 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 153: a β-strand

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: atrial septal defect 5 dilated cardiomyopathy 1R

Similar variants

ACTC1 p.Ile153Thr Uncertain significance ★★ ⚠ same residue
ACTC1 p.Glu101Lys Pathogenic ★★★ 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
ACTC1 c.455-6G>A Uncertain significance ★★ same condition
ACTC1 c.808+1G>C 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/actc1-p-ile153 (accessed [today's date]).

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