KCNC3 p.Pro647=
c.1941G>A · rs777792401 · VCV722276
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.057%, 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 -14 | GERP -2.3 |
| Overall | ||
| CADD | 0.781 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.057%
Admixed American · 29/50,878 alleles
Filtering AF
0.0407%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0353%
Overall
0.00452%
70/1,548,504 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.057% | 1,754 |
| Remaining individualsnot grpmax-eligible | 0.0167% | 5,994 |
| South Asian | 0.00596% | 16,774 |
| African / African-American | 0.00411% | 24,345 |
| Finnishnot grpmax-eligible | 0.00341% | 29,283 |
| European (non-Finnish) | 0.00183% | 54,601 |
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.Pro647=
- Coding
- c.1941G>A
- MANE Select
- NM_004977
- dbSNP
- rs777792401
- Type
- single nucleotide variant
- Location
- chr19:50323012 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI 0.30 (gnomAD)
- Structure
- AlphaFold pLDDT 66.01
Similar variants
- KCNC3 p.Pro647Leu 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-pro647 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown