KCNC3 p.Arg420=
c.1260C>T · rs115066106 · VCV995138
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, 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 -1.6 | GERP -4.3 |
| Overall | ||
| CADD | 2.296 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/74,962 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.000743%
12/1,614,098 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,496 |
| Admixed American | 0.00167% | 60,008 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
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.Arg420=
- Coding
- c.1260C>T
- MANE Select
- NM_004977
- dbSNP
- rs115066106
- Type
- single nucleotide variant
- Location
- chr19:50323693 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
- Residue 420
- a UniProt-annotated variant site (in sca13; dominant negative that induces loss of channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane and alters the localization of the wild-type protein; impairs n-glycosylation; no effect on tetramerization)
Similar variants
- KCNC3 p.Arg420His Pathogenic ★★ same residue
- KCNC3 p.Arg420Cys Uncertain significance ★ ⚠ same residue
- 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-arg420 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown