RBBP8 p.Pro461=
c.1383C>G · rs768585275 · VCV2796177
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, sas)
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 -1.7 | GERP -3.7 |
| Overall | ||
| CADD | 4.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
South Asian · 23/91,070 alleles
Filtering AF
0.0172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0146%
Overall
0.00149%
24/1,614,134 alleles · ultra-rare
exomes 24/1,461,882 · genomes 0/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0253% | 3,960 |
| European (non-Finnish) | 8.47e-05% | 1,180,027 |
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
- RBBP8
- Protein
- p.Pro461=
- Coding
- c.1383C>G
- MANE Select
- NM_002894
- dbSNP
- rs768585275
- Type
- single nucleotide variant
- Location
- chr18:22993210 (GRCh38)
- Gene constraint
- LOEUF 0.981 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 53.73 · 4 PDB
- Residue 461
- the 'disordered' region
Similar variants
- RBBP8 p.Gln47Ter Likely pathogenic ★★ same type
- RBBP8 c.2455-4T>G Uncertain significance ★★ same type
- RBBP8 c.2596+3G>A Uncertain significance ★★ same type
- RBBP8 p.Ala833Asp Uncertain significance ★★ ⚠ same type
- RBBP8 p.Arg110Gln Uncertain significance ★★ ⚠ same type
- RBBP8 p.Arg110Trp Uncertain significance ★★ ⚠ same type
- RBBP8 p.Arg443Gln Uncertain significance ★★ ⚠ same type
- RBBP8 p.Arg502Cys 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/rbbp8-p-pro461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown