EPM2A p.Ser25=
c.75G>C · rs1386842136 · VCV509594
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000905%, nfe)
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 -0.14 | GERP 0.64, phastCons 0.65 |
| Overall | ||
| CADD | 11.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000905%
European (non-Finnish) · 9/994,024 alleles
Filtering AF
0.000426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000309%
Overall
0.000717%
9/1,255,838 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
- EPM2A
- Protein
- p.Ser25=
- Coding
- c.75G>C
- MANE Select
- NM_005670
- dbSNP
- rs1386842136
- Type
- single nucleotide variant
- Location
- chr6:145735424 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 25
- the 'disordered' region; the cbm20 domain; a modified residue (phosphoserine; by ampk); a UniProt-annotated variant site (in melf1; atypical form; does not affect glycogen binding); a β-strand
Similar variants
- EPM2A p.Ser25Ter Pathogenic ★ same residue
- EPM2A c.301+1G>T Pathogenic ★★ same type
- EPM2A c.302-1G>C Pathogenic/Likely pathogenic ★★ same type
- EPM2A c.302-2A>G Pathogenic ★★ same type
- EPM2A p.Arg108Cys Pathogenic/Likely pathogenic ★★ same type
- EPM2A p.Arg171His Pathogenic/Likely pathogenic ★★ same type
- EPM2A p.Arg241Ter Pathogenic/Likely pathogenic ★★ same type
- EPM2A p.Gln293Leu Likely pathogenic ★★ same type
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-ser25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown