ACTN3 p.Pro84=
c.252C>T · rs368835939 · VCV3045587
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.01%, sas)
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 -0.16 | GERP -3.7 |
| Overall | ||
| CADD | 4.209 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.01%
South Asian · 848/84,008 alleles
Filtering AF
0.953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.93%
Overall
0.0585%
899/1,535,584 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.01% | 99 |
| Middle Eastern | 0.106% | 946 |
| Remaining individualsnot grpmax-eligible | 0.0584% | 1,713 |
| Admixed American | 0.00392% | 25,495 |
| African / African-American | 0.00137% | 73,104 |
| European (non-Finnish) | 0.00061% | 163,841 |
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.Pro84=
- Coding
- c.252C>T
- MANE Select
- NM_001104 · reported on NM_001258371
- dbSNP
- rs368835939
- Type
- single nucleotide variant
- Location
- chr11:66546762 (GRCh38)
- Gene constraint
- LOEUF 0.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.61 · 3 PDB
- Residue 84
- the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
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-pro84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown