RHOBTB2 p.Pro263=
c.789G>A · rs763201281 · VCV1600335
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0985%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.97 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 13.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0985%
Admixed American · 59/59,894 alleles
Filtering AF
0.0784%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0711%
Overall
0.00423%
68/1,608,726 alleles · ultra-rare
exomes 63/1,456,590 · genomes 5/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0985% | 1,015 |
| African / African-American | 0.00134% | 74,882 |
| South Asian | 0.0011% | 90,776 |
| European (non-Finnish) | 0.000594% | 168,424 |
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
- RHOBTB2
- Protein
- p.Pro263=
- Coding
- c.789G>A
- MANE Select
- NM_015178
- dbSNP
- rs763201281
- Type
- single nucleotide variant
- Location
- chr8:23007034 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 263
- a UniProt-annotated variant site (found in autosomal recessive neurodevelopmental disorder; likely pathogenic); a UniProt-annotated variant site (found in autosomal recessive neurodevelopmental disorder; uncertain significance)
Similar variants
- RHOBTB2 p.Pro263Ala Uncertain significance ★ ⚠ same residue
- RHOBTB2 p.Pro263Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- RHOBTB2 p.Arg461His Pathogenic/Likely pathogenic ★★ ⚠ same type
- RHOBTB2 p.Arg485Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- RHOBTB2 p.Arg489Gln Pathogenic ★★ ⚠ same type
- RHOBTB2 p.Arg489Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
- RHOBTB2 p.Arg489Trp Pathogenic/Likely pathogenic ★★ same type
- RHOBTB2 p.Arg94Cys Pathogenic/Likely pathogenic ★★ 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/rhobtb2-p-pro263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown