Is PRICKLE2 p.Phe160Cys (c.479T>G) pathogenic?

PRICKLE2 p.Phe160Cys (c.479T>G) is classified Uncertain significance in PRICKLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Phe160Cys (c.479T>G)?

PRICKLE2 p.Phe160Cys (c.479T>G) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Phe160Cys (c.479T>G) in the general population?

PRICKLE2 p.Phe160Cys (c.479T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRICKLE2 p.Phe160Cys (c.479T>G)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

PRICKLE2 p.Phe160Cys

c.479T>G · rs2471173322 · VCV2709756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Progressive myoclonic epilepsy type 5

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 5% in PRICKLE2
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 51 kb · p 7.7e-10 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe160Cys
Coding: c.479T>G
MANE Select: NM_198859
dbSNP: rs2471173322
Type: single nucleotide variant
Location: chr3:64157283 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 160: 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.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
PRICKLE2 p.Ala650Val Uncertain significance ★★ ⚠ same condition
PRICKLE2 p.Ala707Thr 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-phe160cys (accessed [today's date]).

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