Is PRICKLE2 p.Asp368= (c.1104C>T) pathogenic?

PRICKLE2 p.Asp368= (c.1104C>T) is classified Likely benign in PRICKLE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0192%, nfe); Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Asp368= (c.1104C>T)?

PRICKLE2 p.Asp368= (c.1104C>T) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Asp368= (c.1104C>T) in the general population?

PRICKLE2 p.Asp368= (c.1104C>T) is ultra-rare (popmax 0.0192%, nfe) (gnomAD).

PRICKLE2 p.Asp368=

c.1104C>T · rs749983619 · VCV1086442

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0192%, nfe)

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 -3.8	GERP -4.9
Overall
CADD	0.879	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0192% European (non-Finnish) · 226/1,180,054 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0154% 249/1,614,246 alleles · ultra-rare exomes 236/1,461,878 · genomes 13/152,368 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0192%	5,221
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Middle Eastern	0.0165%	6,062
East Asian	0.0134%	7,480
South Asian	0.00439%	22,773
African / African-American	0.00133%	75,070

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.Asp368=
Coding: c.1104C>T
MANE Select: NM_198859
dbSNP: rs749983619
Type: single nucleotide variant
Location: chr3:64147386 (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.Asp368Asn Uncertain significance ★ ⚠ same residue
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

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-asp368 (accessed [today's date]).

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