Is ACTG2 p.Thr195Ile (c.584C>T) pathogenic?

ACTG2 p.Thr195Ile (c.584C>T) is classified Conflicting classifications of pathogenicity in ACTG2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-12-30). AlphaMissense: likely pathogenic (0.9632); Absent from gnomAD v4.1; Associated with ACTG2-related disorder.

What condition is associated with ACTG2 p.Thr195Ile (c.584C>T)?

ACTG2 p.Thr195Ile (c.584C>T) is associated with ACTG2-related disorder, visceral myopathy 1 (ClinVar).

How common is ACTG2 p.Thr195Ile (c.584C>T) in the general population?

ACTG2 p.Thr195Ile (c.584C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTG2 p.Thr195Ile (c.584C>T)?

AlphaMissense predicts likely pathogenic (score 0.9632) — an in-silico prediction, not a clinical call.

ACTG2 p.Thr195Ile

c.584C>T · rs1057520694 · VCV379697

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACTG2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9632	likely pathogenic
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -10.53	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

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: ACTG2
Protein: p.Thr195Ile
Coding: c.584C>T
MANE Select: NM_001615
dbSNP: rs1057520694
Type: single nucleotide variant
Location: chr2:73913617 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 95.46 · 4 PDB
Residue 195: a UniProt-annotated variant site (in vscm1); an α-helix

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

Disease context

ACTG2-related disorder

Also linked: visceral myopathy 1

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-thr195ile (accessed [today's date]).

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