KCNC1 p.Pro489=
c.1467G>A · rs370905066 · VCV1160493
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, afr)
Conditions
2
Inborn genetic diseases
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 8.8 | GERP -0.28, phastCons 1 |
| Overall | ||
| CADD | 14.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
African / African-American · 5/74,884 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.00285%
46/1,613,312 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00668% | 14,977 |
| European (non-Finnish) | 0.00348% | 28,768 |
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
- KCNC1
- Protein
- p.Pro489=
- Coding
- c.1467G>A
- MANE Select
- NM_001112741
- dbSNP
- rs370905066
- Type
- single nucleotide variant
- Location
- chr11:17772561 (GRCh38)
- Gene constraint
- LOEUF 0.363 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.51 · 10 PDB
Similar variants
- KCNC1 p.Pro489Leu Uncertain significance ★ ⚠ same residue
- KCNC1 p.Ala421Val Pathogenic/Likely pathogenic ★★ same condition
- KCNC1 p.Arg320His Pathogenic/Likely pathogenic ★★ same condition
- KCNC1 p.Thr399Met Pathogenic/Likely pathogenic ★★ same condition
- KCNC1 p.Val425Met Pathogenic/Likely pathogenic ★★ same condition
- KCNC1 p.Ala360Thr Uncertain significance ★★ ⚠ same condition
- KCNC1 p.Ala418Ser Uncertain significance ★★ ⚠ same condition
- KCNC1 p.Ala510Val Uncertain significance ★★ same condition
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/kcnc1-p-pro489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown