CD40LG p.Glu129=
c.387G>A · rs746052549 · VCV1137810
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00889%, eas)
Conditions
1
hyper-IgM syndrome type 1
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 0.83 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 5.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00889%
East Asian · 3/33,753 alleles
Filtering AF
0.00235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00125%
Overall
0.000414%
5/1,207,862 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00889% | 11,251 |
| European (non-Finnish) | 0.000224% | 446,672 |
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
- CD40LG
- Protein
- p.Glu129=
- Coding
- c.387G>A
- MANE Select
- NM_000074
- dbSNP
- rs746052549
- Type
- single nucleotide variant
- Location
- chrX:136656396 (GRCh38)
- Structure
- AlphaFold pLDDT 82.34 · 8 PDB
- Residue 129
- a UniProt-annotated variant site (in higm1); a β-strand; the thd domain
Similar variants
- CD40LG p.Glu129Ter Pathogenic ★ same residue
- CD40LG p.Glu129fs Pathogenic ★ same residue
- CD40LG p.Glu129Lys Uncertain significance ★ same residue
- CD40LG c.346+5G>A Pathogenic/Likely pathogenic ★★ same condition
- CD40LG c.347-2A>G Pathogenic ★★ same condition
- CD40LG p.Arg11Ter Pathogenic ★★ same condition
- CD40LG p.Cys218Ter Pathogenic ★★ same condition
- CD40LG p.Gln160Ter Pathogenic ★★ 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/cd40lg-p-glu129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown