Is KCNA2 p.Asp280= (c.840C>T) pathogenic?

KCNA2 p.Asp280= (c.840C>T) is classified Likely benign in KCNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Ultra-rare (popmax 0.0111%, eas); Associated with developmental and epileptic encephalopathy, 32.

What condition is associated with KCNA2 p.Asp280= (c.840C>T)?

KCNA2 p.Asp280= (c.840C>T) is associated with developmental and epileptic encephalopathy, 32 (ClinVar).

How common is KCNA2 p.Asp280= (c.840C>T) in the general population?

KCNA2 p.Asp280= (c.840C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

KCNA2 p.Asp280=

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.840C>T · rs571429123 · VCV1548107

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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 -2.3	GERP -5
Overall
CADD	7.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,872 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00149% 24/1,614,164 alleles · ultra-rare exomes 17/1,461,892 · genomes 7/152,272 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,974
Admixed American	0.00333%	30,011
African / African-American	0.00267%	37,515
European (non-Finnish)	0.00119%	84,288
South Asian	0.0011%	91,088

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.Asp280=
Coding: c.840C>T
MANE Select: NM_004974
dbSNP: rs571429123
Type: single nucleotide variant
Location: chr1:110603943 (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.Asp280Asn 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
KCNA2 p.Gly338Glu Pathogenic/Likely pathogenic ★★ same condition
KCNA2 p.Pro405Leu 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/kcna2-p-asp280 (accessed [today's date]).

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