RORB p.Ala238=
c.714G>A · rs138739090 · VCV1599559
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.427%, 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 -10 | GERP -5.7 |
| Overall | ||
| CADD | 0.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.427%
African / African-American · 320/75,004 alleles
Filtering AF
0.388%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.373%
Overall
0.0609%
983/1,613,834 alleles · rare
exomes 736/1,461,580 · genomes 247/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.427% | 234 |
| Ashkenazi Jewishnot grpmax-eligible | 0.416% | 241 |
| Middle Eastern | 0.247% | 404 |
| Admixed American | 0.177% | 566 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| South Asian | 0.0538% | 1,858 |
| East Asian | 0.049% | 2,040 |
| European (non-Finnish) | 0.025% | 4,000 |
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.Ala238=
- Coding
- c.714G>A
- MANE Select
- NM_006914
- dbSNP
- rs138739090
- Type
- single nucleotide variant
- Location
- chr9:74660693 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48
- Residue 238
- the nr lbd domain; a UniProt-annotated variant site (in eig15; loss of subcellular location in the nucleoplasm)
Similar variants
- RORB p.Ala238Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala238 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown