Is CD40LG p.Phe63fs (c.189del) pathogenic?

CD40LG p.Phe63fs (c.189del) is classified Likely pathogenic in CD40LG (ClinVar, Single submitter, 1 submitter; last evaluated 2011-08-18). Absent from gnomAD; Associated with hyper-IgM syndrome type 1.

What condition is associated with CD40LG p.Phe63fs (c.189del)?

CD40LG p.Phe63fs (c.189del) is associated with hyper-IgM syndrome type 1 (ClinVar).

How common is CD40LG p.Phe63fs (c.189del) in the general population?

CD40LG p.Phe63fs (c.189del) is absent from gnomAD (gnomAD).

CD40LG p.Phe63fs

c.189del · rs193922134 · VCV35811

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hyper-IgM syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.8	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CD40LG
Protein: p.Phe63fs
Coding: c.189del
MANE Select: NM_000074
dbSNP: rs193922134
Type: Deletion
Location: chrX:136650295 (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 p.Ala187fs Pathogenic ★★ same condition
CD40LG c.288+20del Benign/Likely benign ★★ same condition
CD40LG c.349_409+2del Likely pathogenic ★ same condition
CD40LG c.409+1del Pathogenic ★ same condition
CD40LG p.Ala215fs Pathogenic ★ same condition
CD40LG p.Asn157fs Pathogenic ★ same condition
CD40LG p.Gln114fs Pathogenic ★ same condition
CD40LG p.Glu129fs 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-phe63fs (accessed [today's date]).

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