Is KCNT1 p.Pro4Arg (c.11C>G) pathogenic?

KCNT1 p.Pro4Arg (c.11C>G) is classified Likely benign in KCNT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-24). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with KCNT1 p.Pro4Arg (c.11C>G)?

KCNT1 p.Pro4Arg (c.11C>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 14, autosomal dominant nocturnal frontal lobe epilepsy 5 (ClinVar).

How common is KCNT1 p.Pro4Arg (c.11C>G) in the general population?

KCNT1 p.Pro4Arg (c.11C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

KCNT1 p.Pro4Arg

c.11C>G · rs747733979 · VCV1046530

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -0.36
Regional constraint	o/e 1.16	unconstrained · MANE · 48 kb · p 0.042 · regional, not allelic
Overall
CADD	17.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,586 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000373% 6/1,608,620 alleles · very rare exomes 5/1,456,524 · genomes 1/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,586
European (non-Finnish)	0.000425%	235,525

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.Pro4Arg
Coding: c.11C>G
MANE Select: NM_020822
dbSNP: rs747733979
Type: single nucleotide variant
Location: chr9:135702269 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 6 PDB
Residue 4: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 14 autosomal dominant nocturnal frontal lobe epilepsy 5

Similar variants

KCNT1 p.Pro4Ser Conflicting classifications of pathogenicity ★ 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-pro4arg (accessed [today's date]).

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