Is KCNT1 p.Pro820= (c.2460A>G) pathogenic?

KCNT1 p.Pro820= (c.2460A>G) is classified Likely benign in KCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Very rare (popmax 0.00534%, afr); Associated with autosomal dominant nocturnal frontal lobe epilepsy 5.

What condition is associated with KCNT1 p.Pro820= (c.2460A>G)?

KCNT1 p.Pro820= (c.2460A>G) is associated with autosomal dominant nocturnal frontal lobe epilepsy 5, developmental and epileptic encephalopathy, 14 (ClinVar).

How common is KCNT1 p.Pro820= (c.2460A>G) in the general population?

KCNT1 p.Pro820= (c.2460A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Sleep-related hypermotor epilepsy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KCNT1 p.Pro820=

c.2460A>G · rs1219349050 · VCV1566853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

autosomal dominant nocturnal frontal lobe epilepsy 5

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 -15	GERP -3.9
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,896 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,920 alleles · very rare exomes 2/1,461,754 · genomes 2/152,166 · joint denominator

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.Pro820=
Coding: c.2460A>G
MANE Select: NM_020822
dbSNP: rs1219349050
Type: single nucleotide variant
Location: chr9:135777448 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 6 PDB
Residue 820: a β-strand; the rck n-terminal 2 domain; a binding site

Full KCNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nocturnal frontal lobe epilepsy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 14

For Sleep-related hypermotor epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

KCNT1 p.Pro820Leu Likely pathogenic ★ same residue
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

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-pro820 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown