Is KCNA2 p.Pro382= (c.1146G>A) pathogenic?

KCNA2 p.Pro382= (c.1146G>A) is classified Likely benign in KCNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Ultra-rare (popmax 0.016%, afr); Associated with developmental and epileptic encephalopathy, 32.

What condition is associated with KCNA2 p.Pro382= (c.1146G>A)?

KCNA2 p.Pro382= (c.1146G>A) is associated with developmental and epileptic encephalopathy, 32 (ClinVar).

How common is KCNA2 p.Pro382= (c.1146G>A) in the general population?

KCNA2 p.Pro382= (c.1146G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

KCNA2 p.Pro382=

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.1146G>A · rs370714935 · VCV1084450

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

developmental and epileptic encephalopathy, 32

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 -6	GERP -4.6
Overall
CADD	0.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/75,008 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00675% 109/1,614,076 alleles · ultra-rare exomes 100/1,461,824 · genomes 9/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,251
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00763%	13,111
South Asian	0.0011%	91,068

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: KCNA2
Protein: p.Pro382=
Coding: c.1146G>A
MANE Select: NM_004974
dbSNP: rs370714935
Type: single nucleotide variant
Location: chr1:110603637 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.01

Full KCNA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 32 — 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

KCNA2 p.Pro382Arg Uncertain significance ★★ ⚠ same residue
KCNA2 p.Pro382Leu Uncertain significance ★★ ⚠ same residue
KCNA2 p.Pro382Ala Uncertain significance ★ ⚠ same residue
KCNA2 p.Ala262Val Pathogenic/Likely pathogenic ★★ same condition
KCNA2 p.Arg294His Pathogenic/Likely pathogenic ★★ same condition
KCNA2 p.Arg297Gln Pathogenic ★★ same condition
KCNA2 p.Arg297Trp Pathogenic ★★ same condition
KCNA2 p.Gln213Ter 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/kcna2-p-pro382 (accessed [today's date]).

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