RHOBTB2 p.Ser288=
c.864T>C · rs2466178 · VCV1246847
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 95.9%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
developmental and epileptic encephalopathy, 64
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 1.5 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 11.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
95.9%
East Asian · 43,017/44,840 alleles
Filtering AF
95.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 94.9%
Overall
84%
1,353,107/1,609,980 alleles · common
exomes 1,223,101/1,457,840 · genomes 130,006/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 95.9% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 91.5% | 1 |
| Middle Eastern | 88.9% | 1 |
| African / African-American | 87.4% | 1 |
| Admixed American | 87% | 1 |
| South Asian | 85.9% | 1 |
| Remaining individualsnot grpmax-eligible | 84.5% | 1 |
| Amishnot grpmax-eligible | 84% | 1 |
| European (non-Finnish) | 82.9% | 1 |
| Finnishnot grpmax-eligible | 82.4% | 1 |
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.Ser288=
- Coding
- c.864T>C
- MANE Select
- NM_015178
- dbSNP
- rs2466178
- Type
- single nucleotide variant
- Location
- chr8:23007109 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 288
- the btb 1 domain; 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.Ser288Thr Uncertain significance ★ ⚠ same residue
- RHOBTB2 p.Arg461His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RHOBTB2 p.Arg485Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RHOBTB2 p.Arg489Gln Pathogenic ★★ ⚠ same condition
- RHOBTB2 p.Arg489Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RHOBTB2 p.Arg489Trp Pathogenic/Likely pathogenic ★★ same condition
- RHOBTB2 p.Arg94Cys Pathogenic/Likely pathogenic ★★ same condition
- RHOBTB2 p.Asn488Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
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-ser288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown