RHOBTB2 p.Pro246=
c.738C>T · rs139893760 · VCV1530749
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0569%, nfe)
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 0.032 | GERP -1.7, phastCons 0.78 |
| Overall | ||
| CADD | 12.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0569%
European (non-Finnish) · 671/1,179,878 alleles
Filtering AF
0.0533%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0519%
Overall
0.0437%
704/1,610,540 alleles · ultra-rare
exomes 676/1,458,262 · genomes 28/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0569% | 1,758 |
| Middle Eastern | 0.033% | 3,030 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,679 |
| African / African-American | 0.0133% | 7,503 |
| Admixed American | 0.00833% | 12,002 |
| East Asian | 0.00669% | 14,957 |
| Finnishnot grpmax-eligible | 0.00165% | 60,708 |
| South Asian | 0.0011% | 91,038 |
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.Pro246=
- Coding
- c.738C>T
- MANE Select
- NM_015178
- dbSNP
- rs139893760
- Type
- single nucleotide variant
- Location
- chr8:23006983 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 246
- 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-pro246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown