Is EPM2A p.Phe84= (c.252C>T) pathogenic?

EPM2A p.Phe84= (c.252C>T) is classified Likely benign in EPM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). Very rare (popmax 0.000701%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Phe84= (c.252C>T)?

EPM2A p.Phe84= (c.252C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Phe84= (c.252C>T) in the general population?

EPM2A p.Phe84= (c.252C>T) is very rare (popmax 0.000701%, nfe) (gnomAD).

EPM2A p.Phe84=

c.252C>T · rs1362231306 · VCV756722

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000701%, nfe)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.182	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9	GERP 0.81, phastCons 1
Overall
CADD	15.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000701% European (non-Finnish) · 8/1,141,842 alleles

Filtering AF 0.000301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000577% 8/1,386,436 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.Phe84=
Coding: c.252C>T
MANE Select: NM_005670
dbSNP: rs1362231306
Type: single nucleotide variant
Location: chr6:145735247 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 84: the 'disordered' region; the cbm20 domain; a UniProt-annotated variant site (in melf1; affects phosphatase activity and glycogen binding; disrupts the interaction with ppp1r3c); a β-strand

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.Phe84Leu Likely pathogenic ★ 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-phe84 (accessed [today's date]).

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