Is ACTC1 p.Thr262= (c.786A>G) pathogenic?

ACTC1 p.Thr262= (c.786A>G) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Thr262= (c.786A>G)?

ACTC1 p.Thr262= (c.786A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ACTC1 p.Thr262= (c.786A>G) in the general population?

ACTC1 p.Thr262= (c.786A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

ACTC1 p.Thr262=

c.786A>G · VCV3483511

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -20	GERP -4.3
Overall
CADD	0.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Overall 6.2e-05% 1/1,614,062 alleles · very rare exomes 1/1,461,884 · genomes 0/152,178 · 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.Thr262=
Coding: c.786A>G
MANE Select: NM_005159
Type: single nucleotide variant
Location: chr15:34792112 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 262: 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

Similar variants

ACTC1 c.808+3G>A Uncertain significance ★★ same condition
ACTC1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg208Cys Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg208His Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg64Lys Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp159Asn Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp365Asn Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp53Val 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-thr262 (accessed [today's date]).

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