Is PRICKLE1 p.Val36= (c.108C>T) pathogenic?

PRICKLE1 p.Val36= (c.108C>T) is classified Benign/Likely benign in PRICKLE1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-01). Rare (popmax 0.577%, mid); Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Val36= (c.108C>T)?

PRICKLE1 p.Val36= (c.108C>T) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Val36= (c.108C>T) in the general population?

PRICKLE1 p.Val36= (c.108C>T) is rare (popmax 0.577%, mid) (gnomAD).

PRICKLE1 p.Val36=

c.108C>T · rs147268650 · VCV138802

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.577%, mid)

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 -4.9	GERP -3.7
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.577% Middle Eastern · 35/6,062 alleles

Filtering AF 0.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.535%

Overall 0.455% 7,345/1,614,088 alleles · rare exomes 6,781/1,461,842 · genomes 564/152,246 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.71%	17
Middle Easterngrpmax	0.577%	173
European (non-Finnish)	0.551%	181
Remaining individualsnot grpmax-eligible	0.43%	232
South Asian	0.294%	340
Admixed American	0.142%	706
Finnishnot grpmax-eligible	0.119%	842
African / African-American	0.064%	1,563
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
East Asian	0.0111%	8,975

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val36=
Coding: c.108C>T
MANE Select: NM_153026
dbSNP: rs147268650
Type: single nucleotide variant
Location: chr12:42472409 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55
Residue 36: 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

RILP p.Gly36Ser Uncertain significance ★ ⚠ 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-val36 (accessed [today's date]).

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