CRBN p.Phe414=
c.1242T>C · rs199720401 · VCV726282
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 7.11%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.499 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -1.1, phastCons 0.67 |
| Overall | ||
| CADD | 5.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.11%
South Asian · 6,476/91,078 alleles
Filtering AF
6.97%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.91%
Overall
0.429%
6,930/1,614,022 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 7.11% | 14 |
| Remaining individualsnot grpmax-eligible | 0.488% | 205 |
| Middle Eastern | 0.181% | 551 |
| East Asian | 0.0156% | 6,410 |
| African / African-American | 0.0147% | 6,820 |
| European (non-Finnish) | 0.00983% | 10,172 |
| Admixed American | 0.00667% | 14,995 |
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.Phe414=
- Coding
- c.1242T>C
- MANE Select
- NM_016302
- dbSNP
- rs199720401
- Type
- single nucleotide variant
- Location
- chr3:3150952 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 104 PDB
- Residue 414
- the cult domain; a β-strand
Similar variants
- 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
- CRBN p.Met14Leu 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-phe414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown