PRICKLE1 p.Cys603Ter
c.1809T>A · VCV3360919
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.8 | GERP -3.4, phastCons 0.97 |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Cys603Ter
- Coding
- c.1809T>A
- MANE Select
- NM_153026
- Type
- single nucleotide variant
- Location
- chr12:42460496 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 55.55
Similar variants
- PRICKLE1 p.Cys603Arg Uncertain significance ★ ⚠ same residue
- PRICKLE1 c.1639+4C>T Uncertain significance ★★ same type
- PRICKLE1 c.384+6C>A Uncertain significance ★★ same type
- PRICKLE1 p.Ala142Thr Uncertain significance ★★ ⚠ same type
- PRICKLE1 p.Ala145Val Uncertain significance ★★ ⚠ same type
- PRICKLE1 p.Ala34Thr Uncertain significance ★★ ⚠ same type
- PRICKLE1 p.Ala34Val Uncertain significance ★★ ⚠ same type
- PRICKLE1 p.Ala492Thr 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/prickle1-p-cys603ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown