RHOBTB2 p.Pro239=
c.717G>A · rs61759909 · VCV785875
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.46%, 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 -6.6 | GERP -3.7 |
| Overall | ||
| CADD | 1.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.46%
African / African-American · 1,842/74,838 alleles
Filtering AF
2.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.33%
Overall
0.163%
2,629/1,611,000 alleles · low-frequency
exomes 1,518/1,459,224 · genomes 1,111/151,776 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.46% | 41 |
| Middle Eastern | 0.495% | 202 |
| Admixed American | 0.299% | 335 |
| Remaining individualsnot grpmax-eligible | 0.279% | 359 |
| European (non-Finnish) | 0.0331% | 3,018 |
| South Asian | 0.0132% | 7,584 |
| East Asian | 0.00223% | 44,866 |
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.Pro239=
- Coding
- c.717G>A
- MANE Select
- NM_015178
- dbSNP
- rs61759909
- Type
- single nucleotide variant
- Location
- chr8:23006962 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 239
- 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.Pro239Leu Likely benign ★★ 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
- RHOBTB2 p.Asn488Asp 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-pro239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown