RHOBTB2 p.Phe345=
c.1035T>C · rs1810994534 · VCV2985830
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0986%, mid)
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 | GERP -0.54, phastCons 0.003 |
| Overall | ||
| CADD | 6.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0986%
Middle Eastern · 6/6,084 alleles
Filtering AF
0.0429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.000496%
8/1,613,478 alleles · ultra-rare
exomes 7/1,461,312 · genomes 1/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0986% | 1,014 |
| South Asian | 0.0022% | 45,528 |
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.Phe345=
- Coding
- c.1035T>C
- MANE Select
- NM_015178
- dbSNP
- rs1810994534
- Type
- single nucleotide variant
- Location
- chr8:23007280 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 345
- 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.Phe345Cys Uncertain significance ★ ⚠ 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-phe345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown