Is PRICKLE2 p.Val40= (c.120C>T) pathogenic?

PRICKLE2 p.Val40= (c.120C>T) is classified Likely benign in PRICKLE2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Very rare (popmax 0.00534%, afr); Associated with PRICKLE2-related disorder.

What condition is associated with PRICKLE2 p.Val40= (c.120C>T)?

PRICKLE2 p.Val40= (c.120C>T) is associated with PRICKLE2-related disorder (ClinVar).

How common is PRICKLE2 p.Val40= (c.120C>T) in the general population?

PRICKLE2 p.Val40= (c.120C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

PRICKLE2 p.Val40=

c.120C>T · rs769615303 · VCV3057513

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

PRICKLE2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -4.8, phastCons 1
Overall
CADD	13.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,888 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,946 alleles · very rare exomes 0/1,461,870 · genomes 4/152,076 · joint denominator

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: PRICKLE2
Protein: p.Val40=
Coding: c.120C>T
MANE Select: NM_198859
dbSNP: rs769615303
Type: single nucleotide variant
Location: chr3:64198808 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.41
Residue 40: the pet domain

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

Disease context

PRICKLE2-related disorder

Similar variants

PRICKLE2 c.145-98C>G Uncertain significance ★ same condition
PRICKLE2 c.1660+20422G>A Uncertain significance ★ same condition
PRICKLE2 p.Arg213Ter Uncertain significance ★ same condition
PRICKLE2 p.Phe20Leu Uncertain significance ★ ⚠ same condition
PRICKLE2 p.Ala309Val Uncertain significance ⚠ same condition
PRICKLE2 p.Gln516Ter Uncertain significance same condition
PRICKLE2 p.Ser735Thr Uncertain significance ⚠ same condition
PRICKLE2 c.*4330A>T Uncertain significance ★★ same type

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-val40 (accessed [today's date]).

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