Is PRICKLE1 p.Pro147Ser (c.439C>T) pathogenic?

PRICKLE1 p.Pro147Ser (c.439C>T) is classified Uncertain significance in PRICKLE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-05). AlphaMissense: likely benign (0.0992); Absent from gnomAD v4.1; Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Pro147Ser (c.439C>T)?

PRICKLE1 p.Pro147Ser (c.439C>T) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Pro147Ser (c.439C>T) in the general population?

PRICKLE1 p.Pro147Ser (c.439C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRICKLE1 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

PRICKLE1 p.Pro147Ser

c.439C>T · rs1938202392 · VCV1393181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

epilepsy, progressive myoclonic, 1B

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -6.22	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 13 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	22.0	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: PRICKLE1
Protein: p.Pro147Ser
Coding: c.439C>T
MANE Select: NM_153026
dbSNP: rs1938202392
Type: single nucleotide variant
Location: chr12:42468775 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55
Residue 147: 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-pro147ser (accessed [today's date]).

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