CD40LG p.Ser214=
c.642C>T · rs761216947 · VCV1921551
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00592%, 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 -0.54 | GERP -2.5, phastCons 0.023 |
| Overall | ||
| CADD | 1.807 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00592%
East Asian · 2/33,779 alleles
Filtering AF
0.000981%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00071%
Overall
0.00157%
19/1,209,945 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00592% | 16,889 |
| South Asian | 0.00352% | 28,417 |
| Admixed American | 0.00218% | 45,806 |
| European (non-Finnish) | 0.00156% | 63,927 |
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.Ser214=
- Coding
- c.642C>T
- MANE Select
- NM_000074
- dbSNP
- rs761216947
- Type
- single nucleotide variant
- Location
- chrX:136659271 (GRCh38)
- Structure
- AlphaFold pLDDT 82.34 · 8 PDB
- Residue 214
- the thd domain; a disulfide bond
Similar variants
- 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
- CD40LG p.Gln174Ter Pathogenic/Likely pathogenic ★★ same condition
- CD40LG p.Gln220Ter Pathogenic ★★ same condition
- CD40LG p.Gln90Ter 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-ser214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown