ROR2 p.Ala208=
c.624G>A · VCV3715046
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0385%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.66 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.49 | gain · loss 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.3 |
| Overall | ||
| CADD | 16.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0385%
South Asian · 35/91,018 alleles
Filtering AF
0.0283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00292%
47/1,610,068 alleles · ultra-rare
exomes 40/1,457,738 · genomes 7/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0385% | 2,601 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,211 |
| Finnishnot grpmax-eligible | 0.00164% | 60,798 |
| European (non-Finnish) | 0.000763% | 131,046 |
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.Ala208=
- Coding
- c.624G>A
- MANE Select
- NM_004560
- Type
- single nucleotide variant
- Location
- chr9:91733435 (GRCh38)
- Gene constraint
- LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.09 · 6 PDB
- Residue 208
- an α-helix; the fz domain
Similar variants
- ROR2 p.Ala208Thr Uncertain significance ★ ⚠ same residue
- ROR2 p.Ala208Val Uncertain significance ★ ⚠ 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
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-ala208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown