KCNT2 p.Pro1111=
c.3333A>C · rs760206396 · VCV2639673
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00837%, 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 -0.14 | GERP -3.7, phastCons 0.64 |
| Overall | ||
| CADD | 5.332 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00837%
Admixed American · 5/59,712 alleles
Filtering AF
0.00325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00225%
Overall
0.00292%
47/1,610,548 alleles · very rare
exomes 44/1,458,414 · genomes 3/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00837% | 11,942 |
| European (non-Finnish) | 0.0034% | 29,440 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,546 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,340 |
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
- KCNT2
- Protein
- p.Pro1111=
- Coding
- c.3333A>C
- MANE Select
- NM_198503
- dbSNP
- rs760206396
- Type
- single nucleotide variant
- Location
- chr1:196228299 (GRCh38)
- Gene constraint
- LOEUF 0.744 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.42
Similar variants
- KCNT2 p.Ala609Val Uncertain significance ★★ ⚠ same type
- KCNT2 p.Ala711Val Uncertain significance ★★ ⚠ same type
- KCNT2 p.Arg879Gln Uncertain significance ★★ ⚠ same type
- KCNT2 p.Asn29Lys Uncertain significance ★★ ⚠ same type
- KCNT2 p.Cys484Phe Uncertain significance ★★ ⚠ same type
- KCNT2 p.Leu116Val Uncertain significance ★★ ⚠ same type
- KCNT2 p.Leu536Pro Uncertain significance ★★ ⚠ same type
- KCNT2 p.Met807Val 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/kcnt2-p-pro1111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown