EPM2A p.Thr45Pro
c.133A>C · rs2128649753 · VCV2394183
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000139%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.395 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -1.3 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 108 kb · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 2.857 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000139%
European (non-Finnish) · 1/717,718 alleles
Overall
0.000132%
1/754,742 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.Thr45Pro
- Coding
- c.133A>C
- MANE Select
- NM_005670
- dbSNP
- rs2128649753
- Type
- single nucleotide variant
- Location
- chr6:145735366 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 45
- the cbm20 domain
Similar variants
- 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
- EPM2A p.Glu239Val Uncertain significance ★★ same condition
- EPM2A p.Glu307Lys 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-thr45pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown