Is PRDM8 p.Ala438= (c.1314C>T) pathogenic?

PRDM8 p.Ala438= (c.1314C>T) is classified Likely benign in PRDM8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele; Associated with early-onset Lafora body disease.

What condition is associated with PRDM8 p.Ala438= (c.1314C>T)?

PRDM8 p.Ala438= (c.1314C>T) is associated with early-onset Lafora body disease (ClinVar).

How is PRDM8-related progressive myoclonus epilepsy inherited?

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

PRDM8 p.Ala438=

Q: How common is PRDM8 p.Ala438= (c.1314C>T) in the general population?

PRDM8 p.Ala438= (c.1314C>T) is common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1314C>T · rs188061449 · VCV475666

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.075	GERP -1.8, phastCons 0.69
Overall
CADD	10.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% African / African-American · 3,667/64,044 alleles

Filtering AF 5.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.51%

Overall 0.352% 4,401/1,249,798 alleles · common exomes 1,890/1,098,376 · genomes 2,511/151,422 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.73%	17
Admixed American	0.62%	161
Middle Eastern	0.582%	172
Ashkenazi Jewishnot grpmax-eligible	0.522%	191
Remaining individualsnot grpmax-eligible	0.508%	197
Amishnot grpmax-eligible	0.44%	228
European (non-Finnish)	0.0229%	4,372
South Asian	0.0209%	4,777
Finnishnot grpmax-eligible	0.00304%	32,888

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.Ala438=
Coding: c.1314C>T
MANE Select: NM_001099403
dbSNP: rs188061449
Type: single nucleotide variant
Location: chr4:80202776 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 55.64
Residue 438: the 'disordered' region

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.Ala438Val 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-ala438 (accessed [today's date]).

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