CD40 c.646+45A>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.8%, 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 | ||
| Splice region | donor +45 | near-intronic (+45 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.5 |
| Overall | ||
| CADD | 0.126 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.8%
Admixed American · 6,865/57,980 alleles
Filtering AF
11.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.5%
Overall
1.05%
16,730/1,586,572 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 11.8% | 8 |
| Amishnot grpmax-eligible | 3.62% | 28 |
| Remaining individualsnot grpmax-eligible | 1.04% | 96 |
| European (non-Finnish) | 0.708% | 141 |
| South Asian | 0.456% | 219 |
| African / African-American | 0.369% | 271 |
| Middle Eastern | 0.326% | 307 |
| East Asian | 0.245% | 409 |
| Finnishnot grpmax-eligible | 0.184% | 544 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0444% | 2,250 |
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
- CD40
- Coding
- c.646+45A>C
- MANE Select
- NM_001250
- dbSNP
- rs4813000
- Type
- single nucleotide variant
- Location
- chr20:46128269 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 81.10 · 14 PDB
Similar variants
- CD40 c.256+5G>A Uncertain significance ★★ same type
- CD40 c.*178G>A Uncertain significance ★★ same type
- CD40 c.*547A>T Uncertain significance ★★ same type
- CD40 p.Ala25Ser Uncertain significance ★★ ⚠ same type
- CD40 p.Arg123His Uncertain significance ★★ ⚠ same type
- CD40 p.Asn180Lys Uncertain significance ★★ ⚠ same type
- CD40 p.Glu159Lys Uncertain significance ★★ ⚠ same type
- CD40 p.Ile204Val 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/cd40-c-646-plus-45a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown