Is EPM2A p.Leu29Pro (c.86T>C) pathogenic?

EPM2A p.Leu29Pro (c.86T>C) is classified Uncertain significance in EPM2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-19). Absent from gnomAD v4.1; Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Leu29Pro (c.86T>C)?

EPM2A p.Leu29Pro (c.86T>C) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Leu29Pro (c.86T>C) in the general population?

EPM2A p.Leu29Pro (c.86T>C) is absent from gnomAD v4.1 (gnomAD).

EPM2A p.Leu29Pro

c.86T>C · rs2128649883 · VCV1437770

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,251,754)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.898	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 0.64, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 108 kb · p 0.41 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,251,754). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPM2A
Protein: p.Leu29Pro
Coding: c.86T>C
MANE Select: NM_005670
dbSNP: rs2128649883
Type: single nucleotide variant
Location: chr6:145735413 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 29: the 'disordered' region; the cbm20 domain; an α-helix

Full EPM2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPM2A p.Leu29Val Conflicting classifications of pathogenicity ★ 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-leu29pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown