RORB c.892+8A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.69 | GERP -3.9 |
| Non-coding constraint | Z -0.66 | 1 kb window · o/e 1.05 · regional · uncalibrated |
| Overall | ||
| CADD | 2.583 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
South Asian · 19/91,082 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00143%
23/1,612,970 alleles · ultra-rare
exomes 22/1,460,664 · genomes 1/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0209% | 4,794 |
| Admixed American | 0.00167% | 60,026 |
| European (non-Finnish) | 0.000254% | 393,326 |
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
- Coding
- c.892+8A>G
- MANE Select
- NM_006914
- dbSNP
- rs566716336
- Type
- single nucleotide variant
- Location
- chr9:74662614 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48
Similar variants
- 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
- RORB p.Arg279Trp 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-c-892-plus-8a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown