RORB p.Arg84=
c.252G>A · rs2273975 · VCV1300561
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 24.6%, mid) — too common for a highly-penetrant pathogenic allele
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 4.1 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 9.679 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
24.6%
Middle Eastern · 1,483/6,020 alleles
Filtering AF
23.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 23.2%
Overall
16.4%
263,706/1,609,456 alleles · common
exomes 242,387/1,457,262 · genomes 21,319/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 24.6% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.3% | 4 |
| Finnishnot grpmax-eligible | 22.3% | 4 |
| Amishnot grpmax-eligible | 19.3% | 5 |
| European (non-Finnish) | 17.3% | 6 |
| Remaining individualsnot grpmax-eligible | 16.1% | 6 |
| Admixed American | 14.7% | 7 |
| East Asian | 12.4% | 8 |
| South Asian | 9.81% | 10 |
| African / African-American | 5.17% | 19 |
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.Arg84=
- Coding
- c.252G>A
- MANE Select
- NM_006914
- dbSNP
- rs2273975
- Type
- single nucleotide variant
- Location
- chr9:74642430 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48
- Residue 84
- a UniProt-annotated variant site (in eig15); a DNA-binding region; a UniProt-annotated variant site (in eig15; loss of subcellular location in the nucleoplasm)
Similar variants
- RORB p.Arg84Lys Uncertain significance ★ ⚠ 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-arg84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown