RHOBTB2 p.Pro256=
c.768C>T · rs139789090 · VCV715726
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.12%, 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 0.11 | GERP -1.4, phastCons 0.94 |
| Overall | ||
| CADD | 12.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.12%
Admixed American · 1,270/59,944 alleles
Filtering AF
2.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.98%
Overall
0.0954%
1,535/1,608,628 alleles · low-frequency
exomes 1,344/1,456,378 · genomes 191/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 2.12% | 47 |
| East Asian | 0.192% | 521 |
| Remaining individualsnot grpmax-eligible | 0.0673% | 1,486 |
| South Asian | 0.0462% | 2,163 |
| African / African-American | 0.0267% | 3,751 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 0.00611% | 16,373 |
| Finnishnot grpmax-eligible | 0.00332% | 30,143 |
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.Pro256=
- Coding
- c.768C>T
- MANE Select
- NM_015178
- dbSNP
- rs139789090
- Type
- single nucleotide variant
- Location
- chr8:23007013 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 256
- 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.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
- RHOBTB2 p.Asn488Asp Pathogenic/Likely pathogenic ★★ ⚠ same type
- RHOBTB2 c.1502-1G>A 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/rhobtb2-p-pro256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown