KCND2 p.Arg533=
c.1599A>C · VCV4724476
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.84e-05%)
Conditions
1
Early Myoclonic Encephalopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.011 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 11.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.84e-05%
Overall
6.84e-05%
1/1,461,628 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.Arg533=
- Coding
- c.1599A>C
- MANE Select
- NM_012281
- Type
- single nucleotide variant
- Location
- chr7:120745911 (GRCh38)
- Gene constraint
- LOEUF 0.428 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.28 · 16 PDB
- Residue 533
- the 'important for normal channel activation and inactivation, for interaction with kcnip2, and probably other family members as well' region
Similar variants
- KCND2 p.Arg533Ter Uncertain significance ★★ same residue
- KCND2 p.Arg533Gln Likely benign ★ 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
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-arg533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown