RORB p.Leu73=
c.219A>G · rs772732143 · VCV1599344
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.304%, sas)
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 0.88 | GERP -3.3, phastCons 0.97 |
| Overall | ||
| CADD | 6.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.304%
South Asian · 276/90,810 alleles
Filtering AF
0.274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.263%
Overall
0.0181%
292/1,612,390 alleles · rare
exomes 277/1,460,178 · genomes 15/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.304% | 329 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,605 |
| European (non-Finnish) | 0.00102% | 98,269 |
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
- RORB
- Protein
- p.Leu73=
- Coding
- c.219A>G
- MANE Select
- NM_006914
- dbSNP
- rs772732143
- Type
- single nucleotide variant
- Location
- chr9:74634756 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48
- Residue 73
- a DNA-binding region
Similar variants
- RORB p.Leu73Pro Pathogenic ★ same residue
- RORB c.94-1G>A Pathogenic/Likely pathogenic ★★ same type
- RORB p.Arg214Ter Pathogenic/Likely pathogenic ★★ same type
- RORB p.Arg372Ter Pathogenic ★★ same type
- RORB p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
- RORB p.Ala269Thr Uncertain significance ★★ ⚠ same type
- RORB p.Ala95Thr Uncertain significance ★★ ⚠ same type
- RORB p.Arg214Gln 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/rorb-p-leu73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown