Is ACTG2 p.Glu196Asp (c.588G>T) pathogenic?

ACTG2 p.Glu196Asp (c.588G>T) is classified Likely pathogenic in ACTG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-12). AlphaMissense: likely pathogenic (0.9489); Absent from gnomAD v4.1.

How common is ACTG2 p.Glu196Asp (c.588G>T) in the general population?

ACTG2 p.Glu196Asp (c.588G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTG2 p.Glu196Asp (c.588G>T)?

AlphaMissense predicts likely pathogenic (score 0.9489) — an in-silico prediction, not a clinical call.

ACTG2 p.Glu196Asp

c.588G>T · rs140943831 · VCV427095

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9489	likely pathogenic ✓ concordant with ClinVar
REVEL	0.666	pathogenic-leaning
SaProt	LLR -11.81	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 1.8	GERP -2.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic
Overall
CADD	23.5	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.Glu196Asp
Coding: c.588G>T
MANE Select: NM_001615
dbSNP: rs140943831
Type: single nucleotide variant
Location: chr2:73913621 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 95.46 · 4 PDB
Residue 196: a UniProt-annotated variant site (in vscm1); an α-helix

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

Similar variants

ACTG2 p.Ala205Thr Pathogenic ★★ same type
ACTG2 p.Arg148Cys Likely pathogenic ★★ same type
ACTG2 p.Arg178Cys Pathogenic ★★ same type
ACTG2 p.Arg178His Pathogenic ★★ same type
ACTG2 p.Arg178Leu Pathogenic ★★ same type
ACTG2 p.Arg211Gln Pathogenic/Likely pathogenic ★★ same type
ACTG2 p.Arg257Cys Pathogenic ★★ same type
ACTG2 p.Arg257His Pathogenic ★★ 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/actg2-p-glu196asp (accessed [today's date]).

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