Is ACTB p.Arg183Gly (c.547C>G) pathogenic?

ACTB p.Arg183Gly (c.547C>G) is classified Likely pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-30). AlphaMissense: likely pathogenic (0.9833); Absent from gnomAD v4.1; Associated with ACTB-related disorder.

What condition is associated with ACTB p.Arg183Gly (c.547C>G)?

ACTB p.Arg183Gly (c.547C>G) is associated with ACTB-related disorder (ClinVar).

How common is ACTB p.Arg183Gly (c.547C>G) in the general population?

ACTB p.Arg183Gly (c.547C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Arg183Gly (c.547C>G)?

AlphaMissense predicts likely pathogenic (score 0.9833) — an in-silico prediction, not a clinical call.

ACTB p.Arg183Gly

c.547C>G · rs104894003 · VCV989344

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACTB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9833	likely pathogenic ✓ concordant with ClinVar
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -13.94	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 1.8, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 1,149 bp · p 1.6e-51 · regional, not allelic
Overall
CADD	34.0	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: ACTB
Protein: p.Arg183Gly
Coding: c.547C>G
MANE Select: NM_001101
dbSNP: rs104894003
Type: single nucleotide variant
Location: chr7:5528536 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 183: a UniProt-annotated variant site (in dds1; likely pathogenic; results in reduced actin polymerization rate and increased depolymerization; results in higher atp hydrolysis compared to the wild type; does not affect thermal stability; modifies cell response to latrunculin a); an α-helix

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

Disease context

ACTB-related disorder

Similar variants

ACTB p.Arg183Trp Pathogenic ★★ same residue
ACTB p.Arg183Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTB p.Arg206Gly Likely pathogenic ★★ same condition
ACTB p.His40Tyr Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Val159Ala Likely pathogenic ★★ same condition
ACTB p.Val209Leu Likely pathogenic ★★ same condition
ACTB p.Val209Met Pathogenic/Likely pathogenic ★★ same condition
ACTB p.His101Tyr Uncertain significance ★★ ⚠ 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/actb-p-arg183gly (accessed [today's date]).

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