Is ACTG2 p.Ala23Thr (c.67G>A) pathogenic?

ACTG2 p.Ala23Thr (c.67G>A) is classified Uncertain significance in ACTG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-29). AlphaMissense: likely pathogenic (0.9874); Very rare (popmax 0.000339%, nfe); Associated with visceral myopathy 1.

What condition is associated with ACTG2 p.Ala23Thr (c.67G>A)?

ACTG2 p.Ala23Thr (c.67G>A) is associated with visceral myopathy 1 (ClinVar).

How common is ACTG2 p.Ala23Thr (c.67G>A) in the general population?

ACTG2 p.Ala23Thr (c.67G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Familial visceral myopathy inherited?

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

What do computational predictors say about ACTG2 p.Ala23Thr (c.67G>A)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

ACTG2 p.Ala23Thr

c.67G>A · rs1553394796 · VCV495146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

visceral myopathy 1

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,816 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: ACTG2
Protein: p.Ala23Thr
Coding: c.67G>A
MANE Select: NM_001615
dbSNP: rs1553394796
Type: single nucleotide variant
Location: chr2:73901378 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 95.46 · 4 PDB

Full ACTG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

visceral myopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial visceral myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ACTG2 p.Ala205Thr Pathogenic ★★ same condition
ACTG2 p.Arg148Cys Likely pathogenic ★★ same condition
ACTG2 p.Arg178Cys Pathogenic ★★ same condition
ACTG2 p.Arg178His Pathogenic ★★ same condition
ACTG2 p.Arg178Leu Pathogenic ★★ same condition
ACTG2 p.Arg211Gln Pathogenic/Likely pathogenic ★★ same condition
ACTG2 p.Arg257Cys Pathogenic ★★ same condition
ACTG2 p.Arg257His Pathogenic ★★ 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/actg2-p-ala23thr (accessed [today's date]).

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