Is ACTG1 p.Ala29Thr (c.85G>A) pathogenic?

ACTG1 p.Ala29Thr (c.85G>A) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: likely pathogenic (0.8237); Absent from gnomAD v4.1; Associated with ACTG1-related disorder.

What condition is associated with ACTG1 p.Ala29Thr (c.85G>A)?

ACTG1 p.Ala29Thr (c.85G>A) is associated with ACTG1-related disorder (ClinVar).

How common is ACTG1 p.Ala29Thr (c.85G>A) in the general population?

ACTG1 p.Ala29Thr (c.85G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTG1 p.Ala29Thr (c.85G>A)?

AlphaMissense predicts likely pathogenic (score 0.8237) — an in-silico prediction, not a clinical call.

ACTG1 p.Ala29Thr

c.85G>A · rs782108009 · VCV2632597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8237 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACTG1-related disorder

Computational evidence

Protein change
AlphaMissense	0.8237	likely pathogenic
REVEL	0.718	pathogenic-leaning
SaProt	LLR -13.09	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 5.8	GERP 0.67, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 367 bp · p 2.2e-06 · regional, not allelic
Overall
CADD	31.0	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

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: ACTG1
Protein: p.Ala29Thr
Coding: c.85G>A
MANE Select: NM_001614
dbSNP: rs782108009
Type: single nucleotide variant
Location: chr17:81512270 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 29: a β-strand

Full ACTG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACTG1-related disorder

Similar variants

ACTG1 p.Ala29Val Uncertain significance ★ ⚠ same residue
ACTG1 p.Ala29= Likely benign ★ same residue
ACTG1 p.His40Tyr Likely pathogenic ★★ same condition
ACTG1 p.Met283Val Likely pathogenic ★★ ⚠ same condition
ACTG1 p.Pro264Leu Pathogenic ★★ same condition
ACTG1 p.Pro32Ser Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Pro332Ala Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Pro333Arg Likely 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/actg1-p-ala29thr (accessed [today's date]).

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