CD40 c.*178G>A
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.738%, mid)
Conditions
1
hyper-IgM syndrome type 3
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 -1.4 | GERP -3.2 |
| Non-coding constraint | Z 3.36 | 1 kb window · o/e 0.77 · regional · uncalibrated |
| Overall | ||
| CADD | 1.602 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.738%
Middle Eastern · 21/2,844 alleles
Filtering AF
0.592%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.572%
Overall
0.124%
850/686,298 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.738% | 135 |
| South Asian | 0.645% | 155 |
| Ashkenazi Jewishnot grpmax-eligible | 0.485% | 206 |
| Remaining individualsnot grpmax-eligible | 0.134% | 746 |
| European (non-Finnish) | 0.0653% | 1,531 |
| Admixed American | 0.0611% | 1,637 |
| African / African-American | 0.0123% | 8,154 |
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.*178G>A
- MANE Select
- NM_001250
- dbSNP
- rs565941222
- Type
- single nucleotide variant
- Location
- chr20:46129218 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 81.10 · 14 PDB
Similar variants
- CD40 c.*547A>T Uncertain significance ★★ same condition
- CD40 c.403+20A>G Benign/Likely benign ★★ same condition
- CD40 c.52-15C>T Benign/Likely benign ★★ same condition
- CD40 c.559+36G>C Benign ★★ same condition
- CD40 c.-1T>C Benign/Likely benign ★★ same condition
- CD40 c.*135C>G Benign ★★ same condition
- CD40 c.*316G>C Benign ★★ same condition
- CD40 p.Ala207= Benign/Likely benign ★★ same condition
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-star-178g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown