Is PRICKLE2 p.Ser753= (c.2259G>A) pathogenic?

PRICKLE2 p.Ser753= (c.2259G>A) is classified Likely benign in PRICKLE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-27). Rare (popmax 0.198%, mid); Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Ser753= (c.2259G>A)?

PRICKLE2 p.Ser753= (c.2259G>A) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Ser753= (c.2259G>A) in the general population?

PRICKLE2 p.Ser753= (c.2259G>A) is rare (popmax 0.198%, mid) (gnomAD).

PRICKLE2 p.Ser753=

c.2259G>A · rs769036804 · VCV1081212

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, mid)

Conditions

Progressive myoclonic epilepsy type 5

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 -3.4	GERP -1.2
Overall
CADD	12.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% Middle Eastern · 12/6,062 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0895%

Overall 0.00186% 30/1,614,196 alleles · rare exomes 30/1,461,868 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.198%	505
Admixed American	0.00333%	30,016
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000932%	107,276

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.Ser753=
Coding: c.2259G>A
MANE Select: NM_198859
dbSNP: rs769036804
Type: single nucleotide variant
Location: chr3:64099327 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41

Full PRICKLE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Progressive myoclonic epilepsy type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE2 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala146Val Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala149Ser Uncertain significance ★★ same condition
PRICKLE2 p.Ala309Gly Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala33Ser Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala548Thr Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala650Val Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala707Thr 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-ser753 (accessed [today's date]).

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