Is KCND2 p.Val366Phe (c.1096G>T) pathogenic?

KCND2 p.Val366Phe (c.1096G>T) is classified Pathogenic in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-13). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Val366Phe (c.1096G>T)?

KCND2 p.Val366Phe (c.1096G>T) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Val366Phe (c.1096G>T) in the general population?

KCND2 p.Val366Phe (c.1096G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KCND2 p.Val366Phe (c.1096G>T)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

KCND2 p.Val366Phe

c.1096G>T · rs1472234526 · VCV2007789

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Early Myoclonic Encephalopathy

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic ✓ concordant with ClinVar · top 10% in KCND2
REVEL	0.976	strongly pathogenic-leaning
SaProt	LLR -14.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.17	constrained · MANE · 457 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	34.0	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.Val366Phe
Coding: c.1096G>T
MANE Select: NM_012281
dbSNP: rs1472234526
Type: single nucleotide variant
Location: chr7:120275728 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 366: 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-val366phe (accessed [today's date]).

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