Is PRICKLE1 p.Val166= (c.498C>G) pathogenic?

PRICKLE1 p.Val166= (c.498C>G) is classified Likely benign in PRICKLE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). Very rare (popmax 0.0011%, sas); Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Val166= (c.498C>G)?

PRICKLE1 p.Val166= (c.498C>G) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Val166= (c.498C>G) in the general population?

PRICKLE1 p.Val166= (c.498C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

PRICKLE1 p.Val166=

c.498C>G · rs1555230606 · VCV469513

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

epilepsy, progressive myoclonic, 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 22 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP -0.03, phastCons 1
Overall
CADD	10.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 0.000124% 2/1,614,078 alleles · very rare exomes 2/1,461,878 · genomes 0/152,200 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asiangrpmax	0.0011%	91,080

Remaining individuals 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.Val166=
Coding: c.498C>G
MANE Select: NM_153026
dbSNP: rs1555230606
Type: single nucleotide variant
Location: chr12:42468716 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55
Residue 166: the lim zinc-binding 1 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 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
PRICKLE1 p.Ala506Thr 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-val166 (accessed [today's date]).

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