Is PRICKLE2 p.Ser366= (c.1098A>C) pathogenic?

PRICKLE2 p.Ser366= (c.1098A>C) is classified Likely benign in PRICKLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). Ultra-rare (popmax 0.0164%, mid); Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Ser366= (c.1098A>C)?

PRICKLE2 p.Ser366= (c.1098A>C) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Ser366= (c.1098A>C) in the general population?

PRICKLE2 p.Ser366= (c.1098A>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PRICKLE2 p.Ser366=

c.1098A>C · rs779640034 · VCV1104301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -10
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00118% 19/1,614,156 alleles · ultra-rare exomes 14/1,461,892 · genomes 5/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00333%	30,008
South Asian	0.00329%	30,365
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.000932%	107,278

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.Ser366=
Coding: c.1098A>C
MANE Select: NM_198859
dbSNP: rs779640034
Type: single nucleotide variant
Location: chr3:64147392 (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-ser366 (accessed [today's date]).

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