ROR2 p.Ser557=
c.1671G>A · rs201232887 · VCV284857
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0919%, 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 -12 | GERP -3.8 |
| Overall | ||
| CADD | 0.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0919%
Admixed American · 55/59,818 alleles
Filtering AF
0.0725%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0655%
Overall
0.00965%
155/1,606,272 alleles · ultra-rare
exomes 120/1,453,970 · genomes 35/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0919% | 1,088 |
| Remaining individualsnot grpmax-eligible | 0.0177% | 5,651 |
| East Asian | 0.00894% | 11,189 |
| European (non-Finnish) | 0.00638% | 15,667 |
| South Asian | 0.00555% | 18,011 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00344% | 29,098 |
| Finnishnot grpmax-eligible | 0.00315% | 31,752 |
| African / African-American | 0.00267% | 37,465 |
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.Ser557=
- Coding
- c.1671G>A
- MANE Select
- NM_004560
- dbSNP
- rs201232887
- Type
- single nucleotide variant
- Location
- chr9:91724823 (GRCh38)
- Gene constraint
- LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.09 · 6 PDB
- Residue 557
- a UniProt-annotated variant site (in); the protein kinase domain
Similar variants
- ROR2 p.Ser557Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-ser557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown