Is PRICKLE2 p.Ser595= (c.1785G>A) pathogenic?

PRICKLE2 p.Ser595= (c.1785G>A) is classified Likely benign in PRICKLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). Ultra-rare (popmax 0.0329%, mid); Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Ser595= (c.1785G>A)?

PRICKLE2 p.Ser595= (c.1785G>A) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Ser595= (c.1785G>A) in the general population?

PRICKLE2 p.Ser595= (c.1785G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

PRICKLE2 p.Ser595=

c.1785G>A · rs1216760976 · VCV2063180

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Progressive myoclonic epilepsy type 5

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.4	GERP -5.4
Overall
CADD	10.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000496% 8/1,614,080 alleles · ultra-rare exomes 7/1,461,894 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,090
European (non-Finnish)	0.000339%	295,010

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.Ser595=
Coding: c.1785G>A
MANE Select: NM_198859
dbSNP: rs1216760976
Type: single nucleotide variant
Location: chr3:64099801 (GRCh38)

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

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-ser595 (accessed [today's date]).

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