Is PRICKLE2 p.Ala33Ser (c.97G>T) pathogenic?

PRICKLE2 p.Ala33Ser (c.97G>T) is classified Uncertain significance in PRICKLE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-01). AlphaMissense: ambiguous (0.5419); Absent from gnomAD v4.1; Associated with Progressive myoclonic epilepsy type 5.

What condition is associated with PRICKLE2 p.Ala33Ser (c.97G>T)?

PRICKLE2 p.Ala33Ser (c.97G>T) is associated with Progressive myoclonic epilepsy type 5 (ClinVar).

How common is PRICKLE2 p.Ala33Ser (c.97G>T) in the general population?

PRICKLE2 p.Ala33Ser (c.97G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRICKLE2 p.Ala33Ser (c.97G>T)?

AlphaMissense predicts ambiguous (score 0.5419) — an in-silico prediction, not a clinical call.

PRICKLE2 p.Ala33Ser

c.97G>T · rs2471230304 · VCV2085372

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5419 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Progressive myoclonic epilepsy type 5

Computational evidence

Protein change
AlphaMissense	0.5419	ambiguous
REVEL	0.658	pathogenic-leaning
SaProt	LLR -11.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 51 kb · p 7.7e-10 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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.Ala33Ser
Coding: c.97G>T
MANE Select: NM_198859
dbSNP: rs2471230304
Type: single nucleotide variant
Location: chr3:64198831 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 33: the pet 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.Ala33Val 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.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-ala33ser (accessed [today's date]).

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