Is KCND2 p.Pro78= (c.234A>C) pathogenic?

KCND2 p.Pro78= (c.234A>C) is classified Likely benign in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). Ultra-rare (popmax 0.0495%, mid); Associated with Early Myoclonic Encephalopathy.

What condition is associated with KCND2 p.Pro78= (c.234A>C)?

KCND2 p.Pro78= (c.234A>C) is associated with Early Myoclonic Encephalopathy (ClinVar).

How common is KCND2 p.Pro78= (c.234A>C) in the general population?

KCND2 p.Pro78= (c.234A>C) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

KCND2 p.Pro78=

c.234A>C · rs547897725 · VCV1635449

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 -4.2	GERP -5.2
Overall
CADD	4.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00186% 30/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00833%	12,004
African / African-American	0.00266%	37,529
European (non-Finnish)	0.00102%	98,335

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.Pro78=
Coding: c.234A>C
MANE Select: NM_012281
dbSNP: rs547897725
Type: single nucleotide variant
Location: chr7:120274866 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 78: the 'interaction with kcnip1' region; a turn

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-pro78 (accessed [today's date]).

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