Is ACTA2 p.Gly368fs (c.1103_1110delinsT) pathogenic?

ACTA2 p.Gly368fs (c.11031110delinsT) is classified Uncertain significance in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Associated with Cardiovascular phenotype.

What condition is associated with ACTA2 p.Gly368fs (c.1103_1110delinsT)?

ACTA2 p.Gly368fs (c.1103_1110delinsT) is associated with Cardiovascular phenotype (ClinVar).

ACTA2 p.Gly368fs

c.1103_1110delinsT · VCV3895154

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 (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 1.1, phastCons 1

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

Variant & gene context

Gene: ACTA2
Protein: p.Gly368fs
Coding: c.1103_1110delinsT
MANE Select: NM_001613
Type: Indel
Location: chr10:88935247 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.43

Full ACTA2 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

ACTA2 p.Gly368Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTA2 p.Arg258His Pathogenic/Likely pathogenic ★★ same condition
ACTA2 c.616+5G>C Uncertain significance ★★ same condition
ACTA2 p.Pro166Thr Uncertain significance ★★ ⚠ same condition
ACTA2 p.Ter378Gln Uncertain significance ★★ same condition
ACTA2 p.Asn113Thr Uncertain significance ★ ⚠ same condition
ACTA2 p.Gly38Ile Uncertain significance ★ same type

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/acta2-p-gly368fs (accessed [today's date]).

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