Is PRDM8 p.Arg660= (c.1980G>C) pathogenic?

PRDM8 p.Arg660= (c.1980G>C) is classified Benign in PRDM8 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 61.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with early-onset Lafora body disease.

What condition is associated with PRDM8 p.Arg660= (c.1980G>C)?

PRDM8 p.Arg660= (c.1980G>C) 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.Arg660=

Q: How common is PRDM8 p.Arg660= (c.1980G>C) in the general population?

PRDM8 p.Arg660= (c.1980G>C) is common (popmax 61.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1980G>C · rs12780 · VCV1170071

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 61.8%, eas) — 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 0.02	GERP -5.1
Overall
CADD	7.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.8% East Asian · 27,677/44,786 alleles

Filtering AF 61.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.9%

Overall 28% 451,564/1,612,362 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	61.8%	2
South Asian	36.9%	3
Admixed American	35.6%	3
Finnishnot grpmax-eligible	35.1%	3
Remaining individualsnot grpmax-eligible	29.1%	3
Middle Eastern	27.8%	4
Amishnot grpmax-eligible	27.7%	4
Ashkenazi Jewishnot grpmax-eligible	27%	4
European (non-Finnish)	25.8%	4
African / African-American	19%	5

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.Arg660=
Coding: c.1980G>C
MANE Select: NM_001099403
dbSNP: rs12780
Type: single nucleotide variant
Location: chr4:80203442 (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.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-arg660 (accessed [today's date]).

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