Is PRICKLE2 p.Arg110= (c.330C>T) pathogenic?

PRICKLE2 p.Arg110= (c.330C>T) is classified Conflicting classifications of pathogenicity in PRICKLE2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00891%, eas); Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Arg110= (c.330C>T)?

PRICKLE2 p.Arg110= (c.330C>T) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Arg110= (c.330C>T) in the general population?

PRICKLE2 p.Arg110= (c.330C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

PRICKLE2 p.Arg110=

c.330C>T · rs751122249 · VCV197400

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 -5.5	GERP -4.3
Overall
CADD	2.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,890 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00235% 38/1,613,992 alleles · very rare exomes 35/1,461,872 · genomes 3/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
European (non-Finnish)	0.00254%	39,334
South Asian	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00134%	74,886

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.Arg110=
Coding: c.330C>T
MANE Select: NM_198859
dbSNP: rs751122249
Type: single nucleotide variant
Location: chr3:64160006 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 110: the pet domain

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.Arg110Cys Uncertain significance ★★ ⚠ same residue
PRICKLE2 p.Arg110His 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

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-arg110 (accessed [today's date]).

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