KCNC3 p.Ser591=
c.1773C>T · rs1005301925 · VCV724389
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0255%, amr)
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 -4.1 | GERP -2.2 |
| Overall | ||
| CADD | 0.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0255%
Admixed American · 13/50,908 alleles
Filtering AF
0.0151%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0119%
Overall
0.0019%
29/1,526,924 alleles · ultra-rare
exomes 20/1,374,764 · genomes 9/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0255% | 3,916 |
| African / African-American | 0.0165% | 6,063 |
| East Asian | 0.00245% | 40,828 |
| European (non-Finnish) | 0.000263% | 379,740 |
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.Ser591=
- Coding
- c.1773C>T
- MANE Select
- NM_004977
- dbSNP
- rs1005301925
- Type
- single nucleotide variant
- Location
- chr19:50323180 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
- Residue 591
- the 'disordered' region; a UniProt-annotated variant site (in sca13; uncertain significance; reduces channel activity; shifts the voltage dependence of activation)
Similar variants
- KCNC3 p.Ser591Gly Benign/Likely benign ★★ 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-ser591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown