ACTN3 p.Pro81=
c.243C>G · rs150880895 · VCV3050805
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.07%, afr)
Conditions
1
ACTN3-related disorder
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 -0.52 | GERP -3.7 |
| Overall | ||
| CADD | 3.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.07%
African / African-American · 2,243/73,100 alleles
Filtering AF
2.96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.92%
Overall
0.17%
2,608/1,535,636 alleles · low-frequency
exomes 1,274/1,383,428 · genomes 1,334/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.07% | 33 |
| Admixed American | 0.3% | 333 |
| Remaining individualsnot grpmax-eligible | 0.227% | 441 |
| Middle Eastern | 0.123% | 816 |
| South Asian | 0.00714% | 14,007 |
| European (non-Finnish) | 0.00549% | 18,205 |
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.Pro81=
- Coding
- c.243C>G
- MANE Select
- NM_001104 · reported on NM_001258371
- dbSNP
- rs150880895
- Type
- single nucleotide variant
- Location
- chr11:66546753 (GRCh38)
- Gene constraint
- LOEUF 0.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.61 · 3 PDB
- Residue 81
- the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
Disease context
ACTN3-related disorder
Similar variants
- ACTN3 p.Leu81= Likely benign ★ same residue
- 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
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-pro81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown