Is PRDM8 p.Ala39= (c.117T>C) pathogenic?

PRDM8 p.Ala39= (c.117T>C) is classified Benign in PRDM8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-05). Rare (popmax 0.212%, eas); Associated with early-onset Lafora body disease.

What condition is associated with PRDM8 p.Ala39= (c.117T>C)?

PRDM8 p.Ala39= (c.117T>C) is associated with early-onset Lafora body disease (ClinVar).

How common is PRDM8 p.Ala39= (c.117T>C) in the general population?

PRDM8 p.Ala39= (c.117T>C) is rare (popmax 0.212%, eas) (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.Ala39=

c.117T>C · rs369098269 · VCV542342

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.212%, eas)

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 -0.71	GERP -3.5, phastCons 0.019
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.212% East Asian · 95/44,880 alleles

Filtering AF 0.177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.00954% 154/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.212%	472
Remaining individualsnot grpmax-eligible	0.0448%	2,233
African / African-American	0.0386%	2,588
Admixed American	0.00167%	60,018
European (non-Finnish)	8.47e-05%	1,179,993

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: PRDM8
Protein: p.Ala39=
Coding: c.117T>C
MANE Select: NM_001099403
dbSNP: rs369098269
Type: single nucleotide variant
Location: chr4:80200197 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 55.64
Residue 39: the set domain

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.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
PRDM8 p.Arg448Gln 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-ala39 (accessed [today's date]).

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