ROR2 p.Ser554=
c.1662C>T · VCV4749733
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 1.7 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 6.548 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,806 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00109%
Overall
0.00162%
26/1,605,570 alleles · very rare
exomes 23/1,453,368 · genomes 3/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,903 |
| European (non-Finnish) | 0.00196% | 51,069 |
| African / African-American | 0.00134% | 74,812 |
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
- ROR2
- Protein
- p.Ser554=
- Coding
- c.1662C>T
- MANE Select
- NM_004560
- Type
- single nucleotide variant
- Location
- chr9:91724832 (GRCh38)
- Gene constraint
- LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.09 · 6 PDB
- Residue 554
- the protein kinase domain; a β-strand
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-ser554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown