KCNC2 p.Val343=
c.1029G>T · VCV4822431
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0588%, afr)
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 -4.3 | GERP -5.5 |
| Overall | ||
| CADD | 0.605 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0588%
African / African-American · 44/74,852 alleles
Filtering AF
0.0449%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0401%
Overall
0.0039%
63/1,613,678 alleles · ultra-rare
exomes 37/1,461,696 · genomes 26/151,982 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0588% | 1,701 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,463 |
| Admixed American | 0.00167% | 59,926 |
| European (non-Finnish) | 0.000339% | 294,970 |
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.Val343=
- Coding
- c.1029G>T
- MANE Select
- NM_139137
- Type
- single nucleotide variant
- Location
- chr12:75050976 (GRCh38)
- Gene constraint
- LOEUF 0.666 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 68.26
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-val343 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown