Is KCND2 p.Ser557= (c.1671C>T) pathogenic?

KCND2 p.Ser557= (c.1671C>T) is classified Likely benign in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Very rare (popmax 0.00834%, amr); Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Ser557= (c.1671C>T)?

KCND2 p.Ser557= (c.1671C>T) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Ser557= (c.1671C>T) in the general population?

KCND2 p.Ser557= (c.1671C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

KCND2 p.Ser557=

c.1671C>T · rs369805149 · VCV839555

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

Early Myoclonic Encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.506	indeterminate
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.8	GERP -5.9
Overall
CADD	7.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,964 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000342% 5/1,461,512 alleles · very rare

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.Ser557=
Coding: c.1671C>T
MANE Select: NM_012281
dbSNP: rs369805149
Type: single nucleotide variant
Location: chr7:120745983 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 557: the 'important for normal channel activation and inactivation, for interaction with kcnip2, and probably other family members as well' region

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.Ser557Arg 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-ser557 (accessed [today's date]).

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