Is ACTA2 p.Leu348= (c.1044G>C) pathogenic?

ACTA2 p.Leu348= (c.1044G>C) is classified Likely benign in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). Absent from gnomAD v4.1; Associated with aortic aneurysm, familial thoracic 6.

What condition is associated with ACTA2 p.Leu348= (c.1044G>C)?

ACTA2 p.Leu348= (c.1044G>C) is associated with aortic aneurysm, familial thoracic 6 (ClinVar).

How common is ACTA2 p.Leu348= (c.1044G>C) in the general population?

ACTA2 p.Leu348= (c.1044G>C) is absent from gnomAD v4.1 (gnomAD).

ACTA2 p.Leu348=

Q: How is Multisystemic smooth muscle dysfunction syndrome inherited?

Typically Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

c.1044G>C · rs2494502132 · VCV2818705

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

aortic aneurysm, familial thoracic 6

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Overall
CADD	20.4	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: ACTA2
Protein: p.Leu348=
Coding: c.1044G>C
MANE Select: NM_001613
dbSNP: rs2494502132
Type: single nucleotide variant
Location: chr10:88935313 (GRCh38)

Full ACTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aortic aneurysm, familial thoracic 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multisystemic smooth muscle dysfunction syndrome (Orphanet):

Inheritance: Unknown
Onset: Infancy

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-leu348 (accessed [today's date]).

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