EPM2A p.Leu89=
c.267G>A · rs1197084695 · VCV2163210
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000788%, nfe)
Conditions
1
progressive myoclonus epilepsy
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 0.8 | GERP 0.81, phastCons 0.83 |
| Overall | ||
| CADD | 15.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000788%
European (non-Finnish) · 9/1,142,414 alleles
Filtering AF
0.000371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000269%
Overall
0.000584%
9/1,539,784 alleles · very rare
exomes 8/1,388,072 · genomes 1/151,712 · joint denominator
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
- EPM2A
- Protein
- p.Leu89=
- Coding
- c.267G>A
- MANE Select
- NM_005670
- dbSNP
- rs1197084695
- Type
- single nucleotide variant
- Location
- chr6:145735232 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 89
- the 'disordered' region; the cbm20 domain; a β-strand
Similar variants
- EPM2A c.301+1G>T Pathogenic ★★ same condition
- EPM2A c.302-1G>C Pathogenic/Likely pathogenic ★★ same condition
- EPM2A c.302-2A>G Pathogenic ★★ same condition
- EPM2A p.Arg108Cys Pathogenic/Likely pathogenic ★★ same condition
- EPM2A p.Arg171His Pathogenic/Likely pathogenic ★★ same condition
- EPM2A p.Arg241Ter Pathogenic/Likely pathogenic ★★ same condition
- EPM2A p.Gly279Cys Pathogenic/Likely pathogenic ★★ same condition
- EPM2A p.Gly279Ser Pathogenic/Likely pathogenic ★★ 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/epm2a-p-leu89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown