RORB p.Ser138=
c.414C>T · rs746944144 · VCV2870926
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -4.7 | GERP -5.4 |
| Overall | ||
| CADD | 12.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,024 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,614,186 alleles · very rare
exomes 4/1,461,888 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,024 |
| European (non-Finnish) | 0.000254% | 393,343 |
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.Ser138=
- Coding
- c.414C>T
- MANE Select
- NM_006914
- dbSNP
- rs746944144
- Type
- single nucleotide variant
- Location
- chr9:74642592 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48
- Residue 138
- a UniProt-annotated variant site (in eig15; loss of subcellular location in the nucleoplasm)
Similar variants
- RORB p.Ser138Asn 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-ser138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown