CD40LG p.Val228=
c.684A>G · rs11575983 · VCV461469
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.59%, afr)
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 -0.96 | GERP -3.5 |
| Overall | ||
| CADD | 3.245 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.59%
African / African-American · 2,056/57,212 alleles
Filtering AF
3.46%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.41%
Overall
0.202%
2,443/1,209,319 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.59% | 28 |
| Remaining individualsnot grpmax-eligible | 0.345% | 290 |
| Admixed American | 0.301% | 332 |
| Middle Eastern | 0.0919% | 1,088 |
| South Asian | 0.00882% | 11,342 |
| European (non-Finnish) | 0.00849% | 11,772 |
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.Val228=
- Coding
- c.684A>G
- MANE Select
- NM_000074
- dbSNP
- rs11575983
- Type
- single nucleotide variant
- Location
- chrX:136659313 (GRCh38)
- Structure
- AlphaFold pLDDT 82.34 · 8 PDB
- Residue 228
- the thd domain; a β-strand
Similar variants
- CD40LG p.Val228Leu 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
- CD40LG p.Gln174Ter Pathogenic/Likely pathogenic ★★ same condition
- CD40LG p.Gln220Ter 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-val228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown