Is KCND2 p.Ser113Phe (c.338C>T) pathogenic?

KCND2 p.Ser113Phe (c.338C>T) is classified Uncertain significance in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: ambiguous (0.4819); Absent from gnomAD v4.1; Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Ser113Phe (c.338C>T)?

KCND2 p.Ser113Phe (c.338C>T) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Ser113Phe (c.338C>T) in the general population?

KCND2 p.Ser113Phe (c.338C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCND2 p.Ser113Phe (c.338C>T)?

AlphaMissense predicts ambiguous (score 0.4819) — an in-silico prediction, not a clinical call.

KCND2 p.Ser113Phe

c.338C>T · VCV4709929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Early Myoclonic Encephalopathy

Computational evidence

Protein change
AlphaMissense	0.4819	ambiguous
REVEL	0.514	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 844 bp · p 3.1e-15 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KCND2
Protein: p.Ser113Phe
Coding: c.338C>T
MANE Select: NM_012281
Type: single nucleotide variant
Location: chr7:120274970 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 113: 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.Ser113Cys Uncertain significance ★ ⚠ same residue
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

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-ser113phe (accessed [today's date]).

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