CRBN p.Pro85=
c.255A>G · rs1372218265 · VCV3025879
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.126 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.7 | GERP -4.8 |
| Overall | ||
| CADD | 2.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00041%
6/1,461,874 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Admixed American | 0.00167% | 60,024 |
| European (non-Finnish) | 0.000339% | 295,005 |
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
- CRBN
- Protein
- p.Pro85=
- Coding
- c.255A>G
- MANE Select
- NM_016302
- dbSNP
- rs1372218265
- Type
- single nucleotide variant
- Location
- chr3:3174181 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 104 PDB
- Residue 85
- the lon n-terminal domain
Similar variants
- CRBN p.Pro85Arg Uncertain significance ★ ⚠ same residue
- CRBN p.Arg145Ter Pathogenic ★★ same type
- CRBN p.Cys391Arg Likely pathogenic ★★ same type
- CRBN p.Ser214Ter Likely pathogenic ★★ same type
- CRBN p.Arg373Trp Uncertain significance ★★ ⚠ same type
- CRBN p.Asp313His Uncertain significance ★★ ⚠ same type
- CRBN p.Gln7Arg Uncertain significance ★★ ⚠ same type
- CRBN p.Glu32Lys 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/crbn-p-pro85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown