Is PRDM8 p.Ala596= (c.1788G>C) pathogenic?

PRDM8 p.Ala596= (c.1788G>C) is classified Likely benign in PRDM8 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-11). Absent from gnomAD v4.1; Associated with early-onset Lafora body disease.

What condition is associated with PRDM8 p.Ala596= (c.1788G>C)?

PRDM8 p.Ala596= (c.1788G>C) is associated with early-onset Lafora body disease (ClinVar).

How common is PRDM8 p.Ala596= (c.1788G>C) in the general population?

PRDM8 p.Ala596= (c.1788G>C) is absent from gnomAD v4.1 (gnomAD).

How is PRDM8-related progressive myoclonus epilepsy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRDM8 p.Ala596=

c.1788G>C · rs752184496 · VCV1096644

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

early-onset Lafora body disease

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 -0.66	GERP -4.3, phastCons 0.001
Overall
CADD	6.564	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM8
Protein: p.Ala596=
Coding: c.1788G>C
MANE Select: NM_001099403
dbSNP: rs752184496
Type: single nucleotide variant
Location: chr4:80203250 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 55.64

Full PRDM8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

early-onset Lafora body disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PRDM8-related progressive myoclonus epilepsy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PRDM8 p.Ala596_Ala598dup Uncertain significance ★ same residue
PRDM8 p.Ala372Thr Uncertain significance ★★ ⚠ same condition
PRDM8 p.Ala416Thr Uncertain significance ★★ ⚠ same condition
PRDM8 p.Ala529Val Uncertain significance ★★ ⚠ same condition
PRDM8 p.Ala540Ser Uncertain significance ★★ ⚠ same condition
PRDM8 p.Ala541Ser Uncertain significance ★★ ⚠ same condition
PRDM8 p.Ala546Val Uncertain significance ★★ ⚠ same condition
PRDM8 p.Arg272Trp 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/prdm8-p-ala596 (accessed [today's date]).

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