ACTN2 p.Leu504=
c.1512A>G · rs2102934725 · VCV1284862
Benign/Likely benign
No assertion criteria
Classification
Benign/Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 2.9 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 4.238 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,874 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000206%
3/1,459,740 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,874 |
| European (non-Finnish) | 0.00017% | 589,129 |
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
- ACTN2
- Protein
- p.Leu504=
- Coding
- c.1512A>G
- MANE Select
- NM_001103
- dbSNP
- rs2102934725
- Type
- single nucleotide variant
- Location
- chr1:236747772 (GRCh38)
- Gene constraint
- LOEUF 0.432 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.88 · 18 PDB
- Residue 504
- an α-helix
Similar variants
- ACTN2 p.Leu504Pro Uncertain significance ★ ⚠ same residue
- ACTN2 p.Ala119Thr Pathogenic/Likely pathogenic ★★ same type
- ACTN2 p.Leu727Arg Pathogenic/Likely pathogenic ★★ same type
- ACTN2 p.Thr247Met Likely pathogenic ★★ same type
- ACTN2 c.1107+3G>A Uncertain significance ★★ same type
- ACTN2 c.1108-10A>G Uncertain significance ★★ same type
- ACTN2 c.1255+1G>C Uncertain significance ★★ same type
- ACTN2 c.126+2T>G 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/actn2-p-leu504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown