KCNC3 p.Val419=
c.1257C>T · rs201002118 · VCV2903310
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 -1.2 | GERP -4.3 |
| Overall | ||
| CADD | 0.852 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,062 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0294%
Overall
0.00589%
95/1,614,226 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| European (non-Finnish) | 0.00593% | 16,858 |
| South Asian | 0.00549% | 18,218 |
| African / African-American | 0.00533% | 18,769 |
| Admixed American | 0.005% | 20,009 |
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
- KCNC3
- Protein
- p.Val419=
- Coding
- c.1257C>T
- MANE Select
- NM_004977
- dbSNP
- rs201002118
- Type
- single nucleotide variant
- Location
- chr19:50323696 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
Similar variants
- KCNC3 p.Val419Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- KCNC3 p.Arg420His Pathogenic ★★ same type
- KCNC3 p.Arg423His Pathogenic ★★ same type
- KCNC3 p.Ala295Thr Uncertain significance ★★ ⚠ same type
- KCNC3 p.Ala44Ser Uncertain significance ★★ ⚠ same type
- KCNC3 p.Ala615Val Uncertain significance ★★ ⚠ same type
- KCNC3 p.Ala749Thr Uncertain significance ★★ ⚠ same type
- KCNC3 p.Arg417His 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/kcnc3-p-val419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown