KCNT2 p.Arg528=
c.1582A>C · rs373639174 · VCV740143
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0179%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 4.9, phastCons 1 |
| Overall | ||
| CADD | 10.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0179%
Admixed American · 10/55,734 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.012%
190/1,588,980 alleles · ultra-rare
exomes 179/1,437,234 · genomes 11/151,746 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0179% | 5,573 |
| European (non-Finnish) | 0.0146% | 6,837 |
| Remaining individualsnot grpmax-eligible | 0.0131% | 7,662 |
| African / African-American | 0.00135% | 73,806 |
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.Arg528=
- Coding
- c.1582A>C
- MANE Select
- NM_198503
- dbSNP
- rs373639174
- Type
- single nucleotide variant
- Location
- chr1:196340542 (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-arg528 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown