CD40 c.256+7G>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00449%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +7 | near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.33 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.76, phastCons 1 |
| Non-coding constraint | Z 4.96 | 1 kb window · o/e 0.67 · regional · uncalibrated |
| Overall | ||
| CADD | 11.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00449%
European (non-Finnish) · 53/1,180,042 alleles
Filtering AF
0.0035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00318%
Overall
0.00335%
54/1,614,068 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00449% | 22,265 |
| African / African-American | 0.00133% | 74,942 |
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.256+7G>A
- MANE Select
- NM_001250
- dbSNP
- rs764765069
- Type
- single nucleotide variant
- Location
- chr20:46122365 (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-256-plus-7g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown