ROR2 p.Glu453Ter
c.1357G>T · VCV3724683
Pathogenic
Single submitter
Classification
Pathogenic
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/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 29 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | Δ0.94 | donor gain · deltas |
| Pangolin | Δ0.66 | gain · loss 0.41 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 56.0 | 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
- ROR2
- Protein
- p.Glu453Ter
- Coding
- c.1357G>T
- MANE Select
- NM_004560
- Type
- single nucleotide variant
- Location
- chr9:91726570 (GRCh38)
- Gene constraint
- LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.09 · 6 PDB
Similar variants
- ROR2 c.175+1G>A Likely pathogenic ★★ same type
- ROR2 p.Arg119Ter Pathogenic ★★ same type
- ROR2 p.Arg397Ter Pathogenic ★★ same type
- ROR2 p.Arg442Ter Pathogenic ★★ same type
- ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same type
- ROR2 c.175+3G>T Uncertain significance ★★ same type
- ROR2 c.-102G>T Uncertain significance ★★ same type
- ROR2 c.*135G>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/ror2-p-glu453ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown