KCNC3 p.Phe431=
c.1293C>T · rs752090228 · VCV1419702
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
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 -6.7 | GERP -4.3 |
| Overall | ||
| CADD | 2.369 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,084 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00229%
37/1,614,062 alleles · ultra-rare
exomes 33/1,461,818 · genomes 4/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,693 |
| African / African-American | 0.004% | 24,985 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.00144% | 69,415 |
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.Phe431=
- Coding
- c.1293C>T
- MANE Select
- NM_004977
- dbSNP
- rs752090228
- Type
- single nucleotide variant
- Location
- chr19:50323660 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
Similar variants
- 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
- KCNC3 p.Arg625Ser 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-phe431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown