ROR2 p.Leu408=
c.1222T>C · rs368299545 · VCV758949
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0708%, afr)
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 -0.82 | GERP -3 |
| Overall | ||
| CADD | 2.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0708%
African / African-American · 53/74,894 alleles
Filtering AF
0.0555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0501%
Overall
0.00347%
56/1,613,944 alleles · ultra-rare
exomes 27/1,461,876 · genomes 29/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0708% | 1,413 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| Admixed American | 0.00167% | 59,994 |
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.Leu408=
- Coding
- c.1222T>C
- MANE Select
- NM_004560
- dbSNP
- rs368299545
- Type
- single nucleotide variant
- Location
- chr9:91726705 (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-leu408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown