KCNC2 p.Pro65=
c.195G>A · VCV4821011
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.619%, 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 0.59 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 9.519 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.619%
South Asian · 553/89,366 alleles
Filtering AF
0.576%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.559%
Overall
0.0435%
693/1,591,484 alleles · rare
exomes 664/1,439,290 · genomes 29/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.619% | 162 |
| Remaining individualsnot grpmax-eligible | 0.0716% | 1,397 |
| Middle Eastern | 0.0189% | 5,278 |
| European (non-Finnish) | 0.00794% | 12,588 |
| African / African-American | 0.00271% | 36,835 |
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
- KCNC2
- Protein
- p.Pro65=
- Coding
- c.195G>A
- MANE Select
- NM_139137
- Type
- single nucleotide variant
- Location
- chr12:75207789 (GRCh38)
- Gene constraint
- LOEUF 0.666 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 68.26
- Residue 65
- the 'disordered' region
Similar variants
- KCNC2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
- KCNC2 p.Ala431Val Uncertain significance ★★ ⚠ same type
- KCNC2 p.Cys509Phe Uncertain significance ★★ ⚠ same type
- KCNC2 p.Phe382= Benign/Likely benign ★★ same type
- KCNC2 p.Arg351Lys Pathogenic ★ same type
- KCNC2 p.Glu163Lys Likely pathogenic ★ same type
- KCNC2 p.Glu404Lys Likely pathogenic ★ same type
- KCNC2 p.Leu394Ser 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/kcnc2-p-pro65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown