Is ACTC1 p.Val341fs (c.1022_1025del) pathogenic?

ACTC1 p.Val341fs (c.10221025del) is classified Uncertain significance in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Val341fs (c.1022_1025del)?

ACTC1 p.Val341fs (c.1022_1025del) is associated with Cardiovascular phenotype (ClinVar).

ACTC1 p.Val341fs

c.1022_1025del · VCV3895041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ACTC1
Protein: p.Val341fs
Coding: c.1022_1025del
MANE Select: NM_005159
Type: Microsatellite
Location: chr15:34790521 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 341: 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.809-58TG[21] Conflicting classifications of pathogenicity ★ same condition
ACTC1 p.Val341Leu Uncertain significance ★ ⚠ same residue
ACTC1 p.Val341= Likely benign ★ 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

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-val341fs (accessed [today's date]).

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