ACTN3 p.Leu83=
c.249G>A · rs192076014 · VCV2641992
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.223%, afr)
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 3 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 9.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.223%
African / African-American · 167/74,902 alleles
Filtering AF
0.195%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.185%
Overall
0.0119%
191/1,606,714 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.223% | 449 |
| Middle Eastern | 0.0662% | 1,512 |
| Remaining individualsnot grpmax-eligible | 0.0225% | 4,448 |
| Admixed American | 0.0102% | 9,796 |
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.Leu83=
- Coding
- c.249G>A
- MANE Select
- NM_001104
- dbSNP
- rs192076014
- Type
- single nucleotide variant
- Location
- chr11:66551340 (GRCh38)
- Gene constraint
- LOEUF 0.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.61 · 3 PDB
- Residue 83
- the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
Similar variants
- 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
- ACTN3 p.Ala470Pro 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-leu83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown