Is PRICKLE2 p.Glu509= (c.1527G>A) pathogenic?

PRICKLE2 p.Glu509= (c.1527G>A) is classified Benign/Likely benign in PRICKLE2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-30). Rare (popmax 0.644%, afr); Associated with progressive myoclonus epilepsy.

What condition is associated with PRICKLE2 p.Glu509= (c.1527G>A)?

PRICKLE2 p.Glu509= (c.1527G>A) is associated with progressive myoclonus epilepsy (ClinVar).

How common is PRICKLE2 p.Glu509= (c.1527G>A) in the general population?

PRICKLE2 p.Glu509= (c.1527G>A) is rare (popmax 0.644%, afr) (gnomAD).

PRICKLE2 p.Glu509=

c.1527G>A · rs144455095 · VCV448121

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.644%, afr)

Conditions

progressive myoclonus epilepsy

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 -2.3	GERP 3.9
Overall
CADD	3.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.644% African / African-American · 483/74,976 alleles

Filtering AF 0.597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.578%

Overall 0.039% 629/1,614,016 alleles · rare exomes 295/1,461,802 · genomes 334/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.644%	155
Admixed American	0.158%	632
Remaining individualsnot grpmax-eligible	0.064%	1,563
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,539
European (non-Finnish)	0.000678%	147,495

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: PRICKLE2
Protein: p.Glu509=
Coding: c.1527G>A
MANE Select: NM_198859
dbSNP: rs144455095
Type: single nucleotide variant
Location: chr3:64146963 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 509: the 'disordered' region

Full PRICKLE2 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

PRICKLE2 c.*4330A>T Uncertain significance ★★ same condition
PRICKLE2 p.Ala149Ser Uncertain significance ★★ same condition
PRICKLE2 p.Ala698Thr Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Arg390Gln Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Arg521Cys Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Gly512Asp Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.His445Pro Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.His738Arg 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/prickle2-p-glu509 (accessed [today's date]).

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