EPM2A p.Ala46=
c.138G>C · rs1294023321 · VCV1771515
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000109%)
Conditions
1
Inborn genetic diseases
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 -0.76 | GERP 0.64, phastCons 0.003 |
| Overall | ||
| CADD | 7.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000109%
Overall
0.000109%
1/919,950 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.Ala46=
- Coding
- c.138G>C
- MANE Select
- NM_005670
- dbSNP
- rs1294023321
- Type
- single nucleotide variant
- Location
- chr6:145735361 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 46
- the cbm20 domain; a UniProt-annotated variant site (does not affect glycogen binding)
Similar variants
- EPM2A p.Ala46Pro Benign/Likely benign ★★ same residue
- EPM2A p.Ala46Thr Uncertain significance ★★ same residue
- EPM2A c.301+5T>G Uncertain significance ★★ same condition
- EPM2A p.Ala268Thr Uncertain significance ★★ same condition
- EPM2A p.Ala71Glu Uncertain significance ★★ same condition
- EPM2A p.Arg26Leu Uncertain significance ★★ same condition
- EPM2A p.Asn137Ser Uncertain significance ★★ same condition
- EPM2A p.Asn163Ser 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/epm2a-p-ala46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown