Is CD40LG p.Arg200= (c.600A>G) pathogenic?

CD40LG p.Arg200= (c.600A>G) is classified Benign/Likely benign in CD40LG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0264%, sas); Associated with hyper-IgM syndrome type 1.

What condition is associated with CD40LG p.Arg200= (c.600A>G)?

CD40LG p.Arg200= (c.600A>G) is associated with hyper-IgM syndrome type 1 (ClinVar).

How common is CD40LG p.Arg200= (c.600A>G) in the general population?

CD40LG p.Arg200= (c.600A>G) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

CD40LG p.Arg200=

c.600A>G · rs374246579 · VCV1167674

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Conditions

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
Pangolin	Δ0.69	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.4	GERP -0.65, phastCons 1
Overall
CADD	3.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% South Asian · 15/56,818 alleles

Filtering AF 0.0162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0123% 149/1,209,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,788
Middle Eastern	0.0229%	4,375
European (non-Finnish)	0.0145%	6,883
Remaining individualsnot grpmax-eligible	0.0042%	23,789
Finnishnot grpmax-eligible	0.00214%	46,659

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.Arg200=
Coding: c.600A>G
MANE Select: NM_000074
dbSNP: rs374246579
Type: single nucleotide variant
Location: chrX:136659229 (GRCh38)
Structure: AlphaFold pLDDT 82.34 · 8 PDB
Residue 200: the thd domain; a disulfide bond

Full CD40LG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyper-IgM syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD40LG p.Arg200Ter Pathogenic ★ 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-arg200 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown