Is ACTB p.Arg206Gln (c.617G>A) pathogenic?

ACTB p.Arg206Gln (c.617G>A) is classified Pathogenic/Likely pathogenic in ACTB (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-08-18). AlphaMissense: likely pathogenic (0.9226); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACTB p.Arg206Gln (c.617G>A)?

ACTB p.Arg206Gln (c.617G>A) is associated with Inborn genetic diseases, Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Arg206Gln (c.617G>A) in the general population?

ACTB p.Arg206Gln (c.617G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Arg206Gln (c.617G>A)?

AlphaMissense predicts likely pathogenic (score 0.9226) — an in-silico prediction, not a clinical call.

ACTB p.Arg206Gln

c.617G>A · rs886039472 · VCV265318

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.9226 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9226	likely pathogenic ✓ concordant with ClinVar
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -13.24	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 2.7	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	32.0	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.Arg206Gln
Coding: c.617G>A
MANE Select: NM_001101
dbSNP: rs886039472
Type: single nucleotide variant
Location: chr7:5528466 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 206: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baraitser-Winter syndrome 1

Similar variants

ACTB p.Arg206Trp Pathogenic ★★ same residue
ACTB p.Arg206fs Uncertain significance ★ same residue
ACTB p.Arg206Gly Likely pathogenic ★★ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Ala7Thr Likely pathogenic ★★ same condition
ACTB p.Arg147Cys Pathogenic ★★ same condition
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg196Cys 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/actb-p-arg206gln (accessed [today's date]).

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