Is PRICKLE1 p.Pro38= (c.114G>A) pathogenic?

PRICKLE1 p.Pro38= (c.114G>A) is classified Conflicting classifications of pathogenicity in PRICKLE1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-06-01). Rare (popmax 0.462%, nfe); Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Pro38= (c.114G>A)?

PRICKLE1 p.Pro38= (c.114G>A) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Pro38= (c.114G>A) in the general population?

PRICKLE1 p.Pro38= (c.114G>A) is rare (popmax 0.462%, nfe) (gnomAD).

PRICKLE1 p.Pro38=

c.114G>A · rs141743294 · VCV96505

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.462%, nfe)

Conditions

epilepsy, progressive myoclonic, 1B

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 -20	GERP -3.7
Overall
CADD	0.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.462% European (non-Finnish) · 5,455/1,179,990 alleles

Filtering AF 0.452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.448%

Overall 0.376% 6,075/1,614,046 alleles · rare exomes 5,636/1,461,816 · genomes 439/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.462%	216
Finnishnot grpmax-eligible	0.363%	276
Remaining individualsnot grpmax-eligible	0.338%	296
Ashkenazi Jewishnot grpmax-eligible	0.179%	559
Admixed American	0.085%	1,177
Middle Eastern	0.0825%	1,212
African / African-American	0.0613%	1,631
South Asian	0.0242%	4,139

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: PRICKLE1
Protein: p.Pro38=
Coding: c.114G>A
MANE Select: NM_153026
dbSNP: rs141743294
Type: single nucleotide variant
Location: chr12:42472403 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55
Residue 38: the pet domain

Full PRICKLE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, progressive myoclonic, 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE1 p.Pro38Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PRICKLE1 c.1639+4C>T Uncertain significance ★★ same condition
PRICKLE1 c.384+6C>A Uncertain significance ★★ same condition
PRICKLE1 p.Ala142Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala145Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala492Thr 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/prickle1-p-pro38 (accessed [today's date]).

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