KCNT2 p.Pro842=
c.2526C>T · rs371248112 · VCV3052890
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, 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 -2 | GERP -3.7 |
| Overall | ||
| CADD | 9.593 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,934 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.00341%
55/1,612,398 alleles · very rare
exomes 51/1,460,330 · genomes 4/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,983 |
| East Asian | 0.00447% | 22,381 |
| European (non-Finnish) | 0.00348% | 28,755 |
| South Asian | 0.00329% | 30,350 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,188 |
| African / African-American | 0.00267% | 37,415 |
| Finnishnot grpmax-eligible | 0.00156% | 63,960 |
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.Pro842=
- Coding
- c.2526C>T
- MANE Select
- NM_198503
- dbSNP
- rs371248112
- Type
- single nucleotide variant
- Location
- chr1:196305303 (GRCh38)
- Gene constraint
- LOEUF 0.744 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.42
- Residue 842
- the rck n-terminal 2 domain
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-pro842 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown