KCNA2 p.Arg80=
c.238C>A · VCV4906052
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.4 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 12.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,022 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,044 alleles · very rare
exomes 1/1,461,876 · genomes 1/152,168 · joint denominator
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
- KCNA2
- Protein
- p.Arg80=
- Coding
- c.238C>A
- MANE Select
- NM_004974
- Type
- single nucleotide variant
- Location
- chr1:110604545 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.01
- Residue 80
- the 'tetramerization domain' region
Similar variants
- KCNA2 p.Arg80Trp Uncertain significance ★★ ⚠ same residue
- KCNA2 p.Arg80Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- KCNA2 p.Ala262Val Pathogenic/Likely pathogenic ★★ same type
- KCNA2 p.Arg294His Pathogenic/Likely pathogenic ★★ same type
- KCNA2 p.Arg297Gln Pathogenic ★★ same type
- KCNA2 p.Arg297Trp Pathogenic ★★ same type
- KCNA2 p.Gln213Ter Pathogenic ★★ same type
- KCNA2 p.Gly338Glu Pathogenic/Likely pathogenic ★★ 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/kcna2-p-arg80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown