Is PRICKLE2 p.Pro439= (c.1317C>T) pathogenic?

PRICKLE2 p.Pro439= (c.1317C>T) is classified Conflicting classifications of pathogenicity in PRICKLE2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-10). Very rare (popmax 0.00267%, afr); Associated with progressive myoclonus epilepsy.

What condition is associated with PRICKLE2 p.Pro439= (c.1317C>T)?

PRICKLE2 p.Pro439= (c.1317C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is PRICKLE2 p.Pro439= (c.1317C>T) in the general population?

PRICKLE2 p.Pro439= (c.1317C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

PRICKLE2 p.Pro439=

c.1317C>T · rs745530308 · VCV346474

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 0.00267%, afr)

Conditions

progressive myoclonus epilepsy

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 -5.6	GERP -9.8
Overall
CADD	0.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,858 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,808 alleles · very rare exomes 4/1,461,722 · genomes 4/152,086 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,429
East Asian	0.00223%	44,878
South Asian	0.0022%	45,536
European (non-Finnish)	0.000254%	393,315

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.Pro439=
Coding: c.1317C>T
MANE Select: NM_198859
dbSNP: rs745530308
Type: single nucleotide variant
Location: chr3:64147173 (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 myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE2 p.Pro439Leu 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-pro439 (accessed [today's date]).

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