Is ACTC1 p.Ala323= (c.969T>C) pathogenic?

ACTC1 p.Ala323= (c.969T>C) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy 11.

What condition is associated with ACTC1 p.Ala323= (c.969T>C)?

ACTC1 p.Ala323= (c.969T>C) is associated with hypertrophic cardiomyopathy 11, atrial septal defect 5, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Ala323= (c.969T>C) in the general population?

ACTC1 p.Ala323= (c.969T>C) is absent from gnomAD v4.1 (gnomAD).

ACTC1 p.Ala323=

c.969T>C · rs2504177265 · VCV2170679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.76	GERP -1.2, phastCons 0.97
Overall
CADD	9.857	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.Ala323=
Coding: c.969T>C
MANE Select: NM_005159
dbSNP: rs2504177265
Type: single nucleotide variant
Location: chr15:34791135 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB

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.Ala323Pro Uncertain significance ★★ ⚠ same residue
ACTC1 p.Ala323Ser Uncertain significance ★ ⚠ same residue
ACTC1 p.Ala323Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala323 (accessed [today's date]).

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