ACTN3 p.Arg523=
c.1569G>C · rs755970754 · VCV3141946
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000933%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.5 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 15.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000933%
European (non-Finnish) · 11/1,178,432 alleles
Filtering AF
0.000501%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000683%
11/1,610,228 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
- ACTN3
- Protein
- p.Arg523=
- Coding
- c.1569G>C
- MANE Select
- NM_001104
- dbSNP
- rs755970754
- Type
- single nucleotide variant
- Location
- chr11:66560203 (GRCh38)
- Gene constraint
- LOEUF 0.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.61 · 3 PDB
- Residue 523
- a UniProt-annotated variant site (in)
Similar variants
- ACTN3 p.Arg523Gln Benign same residue
- ACTN3 p.Ala115Asp Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala149Thr Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala251Thr Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala410Pro Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala410Val Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala460Val Uncertain significance ★ ⚠ same type
- ACTN3 p.Ala469Gly Uncertain significance ★ ⚠ 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/actn3-p-arg523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown