UBE2I p.Pro46=
c.138A>G · rs4610 · VCV1249830
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 27.5%, amr) — 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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -3.8 |
| Overall | ||
| CADD | 3.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
27.5%
Admixed American · 16,479/59,962 alleles
Filtering AF
27.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 27%
Overall
15%
241,720/1,613,488 alleles · common
exomes 218,812/1,461,362 · genomes 22,908/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 27.5% | 4 |
| African / African-American | 15.8% | 6 |
| European (non-Finnish) | 15.2% | 7 |
| South Asian | 14.6% | 7 |
| Remaining individualsnot grpmax-eligible | 13.6% | 7 |
| Finnishnot grpmax-eligible | 13.1% | 8 |
| Middle Eastern | 9.03% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 6.91% | 14 |
| Amishnot grpmax-eligible | 5.6% | 18 |
| East Asian | 4.05% | 25 |
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
- UBE2I
- Protein
- p.Pro46=
- Coding
- c.138A>G
- MANE Select
- NM_003345
- dbSNP
- rs4610
- Type
- single nucleotide variant
- Location
- chr16:1314364 (GRCh38)
- Gene constraint
- LOEUF 0.28 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 97.46 · 33 PDB
- Residue 46
- the ubc core domain; a β-strand
Similar variants
- UBE2I c.333+19T>C Benign ★★ same type
- UBE2I c.67-13T>C Benign ★★ same type
- UBE2I p.Glu143Gly 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/ube2i-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown