EPM2A p.Phe192Ser
c.575T>C · rs2128562619 · VCV1362973
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
progressive myoclonus epilepsy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.678 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 108 kb · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EPM2A
- Protein
- p.Phe192Ser
- Coding
- c.575T>C
- MANE Select
- NM_005670
- dbSNP
- rs2128562619
- Type
- single nucleotide variant
- Location
- chr6:145635388 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 192
- the tyrosine-protein phosphatase domain
Similar variants
- EPM2A p.Phe192= Likely benign ★ same residue
- 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
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-phe192ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown