Is PRICKLE2 p.Val164Ile (c.490G>A) pathogenic?

PRICKLE2 p.Val164Ile (c.490G>A) is classified Uncertain significance in PRICKLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-03). AlphaMissense: likely benign (0.0742); Absent from gnomAD v4.1; Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Val164Ile (c.490G>A)?

PRICKLE2 p.Val164Ile (c.490G>A) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Val164Ile (c.490G>A) in the general population?

PRICKLE2 p.Val164Ile (c.490G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRICKLE2 p.Val164Ile (c.490G>A)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

PRICKLE2 p.Val164Ile

c.490G>A · rs886058801 · VCV1490968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Progressive myoclonic epilepsy type 5

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.13, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 51 kb · p 7.7e-10 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRICKLE2
Protein: p.Val164Ile
Coding: c.490G>A
MANE Select: NM_198859
dbSNP: rs886058801
Type: single nucleotide variant
Location: chr3:64157272 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 164: the lim zinc-binding 1 domain

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

Disease context

Progressive myoclonic epilepsy type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE2 p.Val164= Likely benign ★ same residue
PRICKLE2 p.Val164Phe Uncertain significance ★★ ⚠ same residue
PRICKLE2 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala146Val Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala149Ser Uncertain significance ★★ same condition
PRICKLE2 p.Ala309Gly Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala33Ser Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala548Thr 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-val164ile (accessed [today's date]).

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