Is KCND2 p.Ala16= (c.48T>C) pathogenic?

KCND2 p.Ala16= (c.48T>C) is classified Likely benign in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Ultra-rare (popmax 0.0147%, afr); Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Ala16= (c.48T>C)?

KCND2 p.Ala16= (c.48T>C) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Ala16= (c.48T>C) in the general population?

KCND2 p.Ala16= (c.48T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

KCND2 p.Ala16=

c.48T>C · rs141637732 · VCV1137688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Early Myoclonic Encephalopathy

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 3.3	GERP 1.7, phastCons 1
Overall
CADD	13.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,934 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000805% 13/1,613,934 alleles · ultra-rare exomes 7/1,461,792 · genomes 6/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,812
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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: KCND2
Protein: p.Ala16=
Coding: c.48T>C
MANE Select: NM_012281
dbSNP: rs141637732
Type: single nucleotide variant
Location: chr7:120274680 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 16: the 'interaction with kcnip1, kcnip2, and other family members' region; an α-helix

Full KCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Early Myoclonic Encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCND2 p.Pro403Ala Pathogenic/Likely pathogenic ★★ same condition
KCND2 c.1374+3A>G Uncertain significance ★★ same condition
KCND2 c.1468-3C>T Uncertain significance ★★ same condition
KCND2 p.Ala321Val Uncertain significance ★★ ⚠ same condition
KCND2 p.Ala399Ser Uncertain significance ★★ ⚠ same condition
KCND2 p.Arg147His Uncertain significance ★★ ⚠ same condition
KCND2 p.Arg533Ter Uncertain significance ★★ same condition
KCND2 p.Asp153Val Uncertain significance ★★ ⚠ 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/kcnd2-p-ala16 (accessed [today's date]).

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