PRICKLE2 p.Pro158=
c.474G>A · rs771310187 · VCV731322
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0332%, mid)
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 -3.9 | GERP -4.2 |
| Overall | ||
| CADD | 2.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0332%
Middle Eastern · 2/6,024 alleles
Filtering AF
0.00585%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00243%
Overall
0.00118%
19/1,614,164 alleles · ultra-rare
exomes 19/1,461,818 · genomes 0/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0332% | 3,012 |
| African / African-American | 0.00266% | 37,534 |
| Admixed American | 0.00167% | 60,030 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
| European (non-Finnish) | 0.0011% | 90,770 |
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.Pro158=
- Coding
- c.474G>A
- MANE Select
- NM_198859
- dbSNP
- rs771310187
- Type
- single nucleotide variant
- Location
- chr3:64157288 (GRCh38)
- Gene constraint
- LOEUF 0.34 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.41
- Residue 158
- the lim zinc-binding 1 domain
Similar variants
- PRICKLE2 c.*4330A>T Uncertain significance ★★ same type
- PRICKLE2 p.Ala143Thr Uncertain significance ★★ ⚠ same type
- PRICKLE2 p.Ala146Val Uncertain significance ★★ ⚠ same type
- PRICKLE2 p.Ala149Ser Uncertain significance ★★ same type
- PRICKLE2 p.Ala309Gly Uncertain significance ★★ ⚠ same type
- PRICKLE2 p.Ala33Ser Uncertain significance ★★ ⚠ same type
- PRICKLE2 p.Ala548Thr Uncertain significance ★★ ⚠ same type
- PRICKLE2 p.Ala650Val 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-pro158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown