KCNC3 p.Pro34=
c.102A>C · rs189639184 · VCV1529387
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0188%, 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 -0.073 | GERP -2.9 |
| Overall | ||
| CADD | 10.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0188%
Admixed American · 4/21,238 alleles
Filtering AF
0.00638%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00385%
Overall
0.0041%
44/1,073,540 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0188% | 5,309 |
| Remaining individualsnot grpmax-eligible | 0.0103% | 9,716 |
| European (non-Finnish) | 0.00423% | 23,650 |
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.Pro34=
- Coding
- c.102A>C
- MANE Select
- NM_004977
- dbSNP
- rs189639184
- Type
- single nucleotide variant
- Location
- chr19:50328981 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
- Residue 34
- the 'disordered' region; the 'important for normal n-type inactivation' region
Similar variants
- KCNC3 p.Pro34_Pro38del Uncertain significance ★ 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-pro34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown