Is KCNT1 p.Pro712= (c.2136C>T) pathogenic?

KCNT1 p.Pro712= (c.2136C>T) is classified Likely benign in KCNT1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-26). Rare (popmax 0.48%, mid); Associated with developmental and epileptic encephalopathy, 14.

What condition is associated with KCNT1 p.Pro712= (c.2136C>T)?

KCNT1 p.Pro712= (c.2136C>T) is associated with developmental and epileptic encephalopathy, 14, autosomal dominant nocturnal frontal lobe epilepsy 5 (ClinVar).

How common is KCNT1 p.Pro712= (c.2136C>T) in the general population?

KCNT1 p.Pro712= (c.2136C>T) is rare (popmax 0.48%, mid) (gnomAD).

KCNT1 p.Pro712=

c.2136C>T · rs377516058 · VCV384650

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.48%, mid)

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 -20	GERP -2.6
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.48% Middle Eastern · 28/5,832 alleles

Filtering AF 0.341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.294%

Overall 0.0251% 387/1,541,362 alleles · rare exomes 352/1,389,020 · genomes 35/152,342 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.48%	208
Admixed American	0.0823%	1,215
South Asian	0.0772%	1,296
Remaining individualsnot grpmax-eligible	0.0554%	1,806
European (non-Finnish)	0.0182%	5,494
Ashkenazi Jewishnot grpmax-eligible	0.0142%	7,053
African / African-American	0.011%	9,112
Finnishnot grpmax-eligible	0.00173%	57,828

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.Pro712=
Coding: c.2136C>T
MANE Select: NM_020822
dbSNP: rs377516058
Type: single nucleotide variant
Location: chr9:135772842 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 6 PDB

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.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-pro712 (accessed [today's date]).

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