Is ACTN3 p.Arg211Gln (c.632G>A) pathogenic?

ACTN3 p.Arg211Gln (c.632G>A) is classified Benign in ACTN3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). AlphaMissense: likely benign (0.0907); Low-frequency (popmax 3.78%, sas); Associated with ACTN3-related disorder.

What condition is associated with ACTN3 p.Arg211Gln (c.632G>A)?

ACTN3 p.Arg211Gln (c.632G>A) is associated with ACTN3-related disorder (ClinVar).

How common is ACTN3 p.Arg211Gln (c.632G>A) in the general population?

ACTN3 p.Arg211Gln (c.632G>A) is low-frequency (popmax 3.78%, sas) (gnomAD).

What do computational predictors say about ACTN3 p.Arg211Gln (c.632G>A)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

ACTN3 p.Arg211Gln

c.632G>A · rs200452235 · VCV3042256

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.78%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

ACTN3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
SaProt	LLR -11.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.42, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 770 bp · p 0.00011 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 3.78% South Asian · 3,442/91,040 alleles

Filtering AF 3.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.63%

Overall 0.239% 3,860/1,613,734 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.78%	26
Remaining individualsnot grpmax-eligible	0.258%	388
Middle Eastern	0.181%	551
African / African-American	0.175%	572
Admixed American	0.0183%	5,453
European (non-Finnish)	0.00848%	11,799
East Asian	0.00446%	22,428
Finnishnot grpmax-eligible	0.00313%	31,995

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: ACTN3
Protein: p.Arg211Gln
Coding: c.632G>A
MANE Select: NM_001104
dbSNP: rs200452235
Type: single nucleotide variant
Location: chr11:66555204 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.61 · 3 PDB
Residue 211: the calponin-homology (ch) 2 domain; the 'actin-binding' region

Full ACTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACTN3-related disorder

Similar variants

ACTN3 c.1129-8C>T Likely benign same condition
ACTN3 c.1678-8G>A Benign same condition
ACTN3 p.Ala417Ser Benign same condition
ACTN3 p.Ala469= Likely benign same condition
ACTN3 p.Ala492= Likely benign same condition
ACTN3 p.Ala564= Likely benign same condition
ACTN3 p.Ala881Ser Likely benign ⚠ same condition
ACTN3 p.Arg199Gln Likely benign 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/actn3-p-arg211gln (accessed [today's date]).

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