Is ACTG1 p.Arg28Gly (c.82C>G) pathogenic?

ACTG1 p.Arg28Gly (c.82C>G) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: likely pathogenic (0.9856); Very rare (popmax 8.47e-05%, nfe).

How common is ACTG1 p.Arg28Gly (c.82C>G) in the general population?

ACTG1 p.Arg28Gly (c.82C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ACTG1 p.Arg28Gly (c.82C>G)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

ACTG1 p.Arg28Gly

c.82C>G · VCV3359682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic
REVEL	0.692	pathogenic-leaning
SaProt	LLR -14.38	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 2.1	GERP -3.4, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 367 bp · p 2.2e-06 · regional, not allelic
Overall
CADD	26.0	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 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.84e-05% 1/1,461,440 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: ACTG1
Protein: p.Arg28Gly
Coding: c.82C>G
MANE Select: NM_001614
Type: single nucleotide variant
Location: chr17:81512273 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 28: a β-strand

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

Similar variants

ACTG1 p.Arg28Ter Uncertain significance ★ same residue
ACTG1 p.Ala135Val Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Ala204Gly Likely pathogenic ★★ same type
ACTG1 p.Arg183Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg183Trp Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg206Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg210Cys Pathogenic ★★ same type
ACTG1 p.Arg254Trp Pathogenic/Likely 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/actg1-p-arg28gly (accessed [today's date]).

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