CD40 p.Ser49=
c.147T>C · rs541686651 · VCV1586111
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.125%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.33 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.1 |
| Overall | ||
| CADD | 0.636 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.125%
South Asian · 114/91,078 alleles
Filtering AF
0.106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0994%
Overall
0.00756%
122/1,614,110 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.125% | 799 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
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
- Protein
- p.Ser49=
- Coding
- c.147T>C
- MANE Select
- NM_001250
- dbSNP
- rs541686651
- Type
- single nucleotide variant
- Location
- chr20:46122249 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 81.10 · 14 PDB
- Residue 49
- a disulfide bond; a β-strand
Similar variants
- CD40 p.Ser49Asn Uncertain significance ★ ⚠ same residue
- 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
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-p-ser49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown