ACTN1 p.Lys281=
c.843G>A · rs202041611 · VCV2052337
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.404%, sas)
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 4.7 | phastCons 1 |
| Overall | ||
| CADD | 13.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.404%
South Asian · 368/91,080 alleles
Filtering AF
0.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.357%
Overall
0.0237%
383/1,614,126 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.404% | 248 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
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
- ACTN1
- Protein
- p.Lys281=
- Coding
- c.843G>A
- MANE Select
- NM_001130004
- dbSNP
- rs202041611
- Type
- single nucleotide variant
- Location
- chr14:68893667 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.39 · 4 PDB
- Residue 281
- the 'interaction with ddn' region
Similar variants
- ACTN1 p.Arg450Cys Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Glu225Lys Pathogenic ★★ same type
- ACTN1 p.Leu547Pro Likely pathogenic ★★ same type
- ACTN1 p.Val105Ile Pathogenic/Likely pathogenic ★★ same type
- ACTN1 p.Ala255Val Uncertain significance ★★ ⚠ same type
- ACTN1 p.Ala48Val 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/actn1-p-lys281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown