Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.7%, afr) — 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.99 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 10.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.7%
African / African-American · 8,048/74,922 alleles
Filtering AF
10.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.5%
Overall
0.598%
9,638/1,612,868 alleles · common
exomes 5,124/1,460,632 · genomes 4,514/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.7% | 9 |
| Middle Eastern | 0.858% | 117 |
| Remaining individualsnot grpmax-eligible | 0.723% | 138 |
| Admixed American | 0.591% | 169 |
| European (non-Finnish) | 0.0583% | 1,714 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0475% | 2,107 |
| South Asian | 0.0308% | 3,243 |
| East Asian | 0.00223% | 44,880 |
| Finnishnot grpmax-eligible | 0.00156% | 64,002 |
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
- CUL2
- Protein
- p.Arg148=
- Coding
- c.444G>A
- MANE Select
- NM_003591
- dbSNP
- rs7897024
- Type
- single nucleotide variant
- Location
- chr10:35049745 (GRCh38)
- Gene constraint
- LOEUF 0.305 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.02 · 42 PDB
- Residue 148
- an α-helix
Similar variants
- CUL2 c.1110+1G>A Uncertain significance ★ same type
- CUL2 c.-22-2881A>G Uncertain significance ★ same type
- CUL2 c.-2C>A Uncertain significance ★ same type
- CUL2 p.Ala403Val Uncertain significance ★ ⚠ same type
- CUL2 p.Ala522Val Uncertain significance ★ ⚠ same type
- CUL2 p.Ala634Ser Uncertain significance ★ ⚠ same type
- CUL2 p.Ala671Ser Uncertain significance ★ ⚠ same type
- CUL2 p.Ala671Val 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/cul2-p-arg148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown