Is KCND2 p.Ser391= (c.1173G>A) pathogenic?

KCND2 p.Ser391= (c.1173G>A) is classified Likely benign in KCND2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0267%, amr); Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Ser391= (c.1173G>A)?

KCND2 p.Ser391= (c.1173G>A) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Ser391= (c.1173G>A) in the general population?

KCND2 p.Ser391= (c.1173G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

KCND2 p.Ser391=

c.1173G>A · rs367909110 · VCV1081873

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

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 -9.5	GERP -5.8
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/59,956 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00242% 39/1,613,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,747
Middle Eastern	0.0165%	6,062
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,474
East Asian	0.00223%	44,848
European (non-Finnish)	0.0011%	90,744

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.Ser391=
Coding: c.1173G>A
MANE Select: NM_012281
dbSNP: rs367909110
Type: single nucleotide variant
Location: chr7:120732960 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 391: 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.Ser391Leu 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-ser391 (accessed [today's date]).

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