CD40LG p.Arg200Ter
c.598A>T · rs2148553738 · VCV1413373
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hyper-IgM syndrome type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP -0.14, phastCons 1 |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CD40LG
- Protein
- p.Arg200Ter
- Coding
- c.598A>T
- MANE Select
- NM_000074
- dbSNP
- rs2148553738
- Type
- single nucleotide variant
- Location
- chrX:136659227 (GRCh38)
- Structure
- AlphaFold pLDDT 82.34 · 8 PDB
- Residue 200
- the thd domain; a disulfide bond
Similar variants
- CD40LG p.Arg200= Benign/Likely benign ★★ 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-arg200ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown