Is KCNT1 p.Phe80= (c.240C>T) pathogenic?

KCNT1 p.Phe80= (c.240C>T) is classified Likely benign in KCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). Very rare (popmax 0.00319%, eas); Associated with developmental and epileptic encephalopathy, 14.

What condition is associated with KCNT1 p.Phe80= (c.240C>T)?

KCNT1 p.Phe80= (c.240C>T) is associated with developmental and epileptic encephalopathy, 14, autosomal dominant nocturnal frontal lobe epilepsy 5 (ClinVar).

How common is KCNT1 p.Phe80= (c.240C>T) in the general population?

KCNT1 p.Phe80= (c.240C>T) is very rare (popmax 0.00319%, eas) (gnomAD).

KCNT1 p.Phe80=

c.240C>T · rs1554763398 · VCV696658

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00319%, eas)

Conditions

developmental and epileptic encephalopathy, 14

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 0.15	GERP -2.5
Overall
CADD	12.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00319% East Asian · 1/31,336 alleles

Filtering AF 7.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000309% 4/1,292,660 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00319%	31,336
European (non-Finnish)	0.000277%	361,505

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.Phe80=
Coding: c.240C>T
MANE Select: NM_020822
dbSNP: rs1554763398
Type: single nucleotide variant
Location: chr9:135714706 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 6 PDB
Residue 80: an α-helix

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

Disease context

developmental and epileptic encephalopathy, 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nocturnal frontal lobe epilepsy 5

Similar variants

KCNT1 p.Phe80Leu Uncertain significance ★★ 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-phe80 (accessed [today's date]).

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