Is KCNB1 p.Pro2= (c.6G>A) pathogenic?

KCNB1 p.Pro2= (c.6G>A) is classified Likely benign in KCNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Very rare (popmax 0.00254%, amr); Associated with developmental and epileptic encephalopathy, 26.

What condition is associated with KCNB1 p.Pro2= (c.6G>A)?

KCNB1 p.Pro2= (c.6G>A) is associated with developmental and epileptic encephalopathy, 26 (ClinVar).

How common is KCNB1 p.Pro2= (c.6G>A) in the general population?

KCNB1 p.Pro2= (c.6G>A) is very rare (popmax 0.00254%, amr) (gnomAD).

KCNB1 p.Pro2=

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

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

c.6G>A · rs1419833676 · VCV1962787

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00254%, amr)

Conditions

developmental and epileptic encephalopathy, 26

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 7.4	GERP -0.48, phastCons 1
Overall
CADD	17.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% Admixed American · 1/39,338 alleles

Overall 6.91e-05% 1/1,447,184 alleles · very rare exomes 1/1,294,940 · genomes 0/152,244 · 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: KCNB1
Protein: p.Pro2=
Coding: c.6G>A
MANE Select: NM_004975
dbSNP: rs1419833676
Type: single nucleotide variant
Location: chr20:49482475 (GRCh38)
Gene constraint: LOEUF 0.309 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.90 · 6 PDB
Residue 2: the 'disordered' region

Full KCNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

KCNB1 p.Pro2Arg Benign ★ same residue
KCNB1 p.Pro2Gln Likely benign ★ same residue
KCNB1 p.Pro2Ser Likely benign ★ same residue
KCNB1 p.Ala406Val Likely pathogenic ★★ same condition
KCNB1 p.Arg303Gln Likely pathogenic ★★ same condition
KCNB1 p.Arg306Cys Pathogenic ★★ same condition
KCNB1 p.Arg312Cys Pathogenic/Likely pathogenic ★★ same condition
KCNB1 p.Arg312His 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/kcnb1-p-pro2 (accessed [today's date]).

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