Is PRICKLE2 p.Arg148= (c.444C>T) pathogenic?

PRICKLE2 p.Arg148= (c.444C>T) is classified Benign/Likely benign in PRICKLE2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.389%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with PRICKLE2 p.Arg148= (c.444C>T)?

PRICKLE2 p.Arg148= (c.444C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is PRICKLE2 p.Arg148= (c.444C>T) in the general population?

PRICKLE2 p.Arg148= (c.444C>T) is rare (popmax 0.389%, nfe) (gnomAD).

PRICKLE2 p.Arg148=

c.444C>T · rs146538069 · VCV197904

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.389%, nfe)

Conditions

progressive myoclonus epilepsy

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 -6.6	GERP -4
Overall
CADD	1.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.389% European (non-Finnish) · 4,593/1,180,032 alleles

Filtering AF 0.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.376%

Overall 0.307% 4,950/1,613,902 alleles · rare exomes 4,667/1,461,578 · genomes 283/152,324 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.389%	257
Remaining individualsnot grpmax-eligible	0.254%	393
Admixed American	0.113%	883
Finnishnot grpmax-eligible	0.0625%	1,601
African / African-American	0.06%	1,668
South Asian	0.0362%	2,759
East Asian	0.0223%	4,488
Middle Eastern	0.0171%	5,840
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Arg148=
Coding: c.444C>T
MANE Select: NM_198859
dbSNP: rs146538069
Type: single nucleotide variant
Location: chr3:64157318 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 148: a UniProt-annotated variant site (found in patients with severe progressive myoclonic epilepsy; uncertain significance; results in increased protein activity when associated with i-153; less active in stimulating calcium release when associated with i-153); the lim zinc-binding 1 domain

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

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE2 p.Arg148Cys Uncertain significance ★ ⚠ same residue
PRICKLE2 c.*4330A>T Uncertain significance ★★ same condition
PRICKLE2 p.Ala149Ser Uncertain significance ★★ same condition
PRICKLE2 p.Ala698Thr Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Arg390Gln Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Arg521Cys Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Gly512Asp Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.His445Pro 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-arg148 (accessed [today's date]).

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