Is CD40LG p.Asn83= (c.249C>T) pathogenic?

CD40LG p.Asn83= (c.249C>T) is classified Likely benign in CD40LG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-14). Very rare (popmax 0.00296%, eas); Associated with hyper-IgM syndrome type 1.

What condition is associated with CD40LG p.Asn83= (c.249C>T)?

CD40LG p.Asn83= (c.249C>T) is associated with hyper-IgM syndrome type 1 (ClinVar).

How common is CD40LG p.Asn83= (c.249C>T) in the general population?

CD40LG p.Asn83= (c.249C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

CD40LG p.Asn83=

c.249C>T · rs761769948 · VCV2788528

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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
Constraint at this position
Conservation	phyloP 2.6	GERP 1.8, phastCons 1
Overall
CADD	9.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,793 alleles

Overall 0.000275% 3/1,092,213 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,793
Remaining individualsnot grpmax-eligible	0.00211%	47,421
European (non-Finnish)	0.000112%	890,298

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.Asn83=
Coding: c.249C>T
MANE Select: NM_000074
dbSNP: rs761769948
Type: single nucleotide variant
Location: chrX:136650358 (GRCh38)
Structure: AlphaFold pLDDT 82.34 · 8 PDB

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 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-asn83 (accessed [today's date]).

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