KCNT1 p.Phe481=
c.1443C>T · rs576446992 · VCV388593
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0497%, mid)
Conditions
3
Inborn genetic diseases
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 -13 | GERP -3.6 |
| Overall | ||
| CADD | 5.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0497%
Middle Eastern · 3/6,040 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.00267%
43/1,613,402 alleles · ultra-rare
exomes 29/1,461,082 · genomes 14/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0497% | 2,013 |
| Admixed American | 0.02% | 5,001 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| African / African-American | 0.00533% | 18,763 |
| East Asian | 0.00446% | 22,429 |
| European (non-Finnish) | 0.00153% | 65,551 |
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
- KCNT1
- Protein
- p.Phe481=
- Coding
- c.1443C>T
- MANE Select
- NM_020822
- dbSNP
- rs576446992
- Type
- single nucleotide variant
- Location
- chr9:135768870 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 6 PDB
- Residue 481
- the rck n-terminal 1 domain
Similar variants
- KCNT1 p.Ala477Thr Pathogenic/Likely pathogenic ★★ same condition
- KCNT1 p.Ala934Ser Pathogenic/Likely pathogenic ★★ same condition
- KCNT1 p.Ala934Thr Pathogenic ★★ same condition
- KCNT1 p.Ala966Thr Pathogenic/Likely pathogenic ★★ same condition
- KCNT1 p.Arg262Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- KCNT1 p.Arg356Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- KCNT1 p.Arg398Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- KCNT1 p.Arg428Gln Pathogenic ★★ ⚠ same condition
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/kcnt1-p-phe481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown