Is ACTC1 p.Leu144= (c.430C>T) pathogenic?

ACTC1 p.Leu144= (c.430C>T) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). Very rare (popmax 0.000169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Leu144= (c.430C>T)?

ACTC1 p.Leu144= (c.430C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ACTC1 p.Leu144= (c.430C>T) in the general population?

ACTC1 p.Leu144= (c.430C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

ACTC1 p.Leu144=

c.430C>T · VCV3825767

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 5.1	GERP 2.3, phastCons 1
Overall
CADD	11.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,994 alleles · very rare

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.Leu144=
Coding: c.430C>T
MANE Select: NM_005159
Type: single nucleotide variant
Location: chr15:34793269 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 144: 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 p.Leu144Arg Uncertain significance ★ ⚠ same residue
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

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-leu144 (accessed [today's date]).

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