Is CD27 p.Gln134fs (c.399del) pathogenic?

CD27 p.Gln134fs (c.399del) is classified Pathogenic in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Gln134fs (c.399del)?

CD27 p.Gln134fs (c.399del) is associated with lymphoproliferative syndrome 2 (ClinVar).

CD27 p.Gln134fs

Q: How is Combined immunodeficiency due to CD27 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.399del · VCV3657123

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.39	GERP 0.99

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

Variant & gene context

Gene: CD27
Protein: p.Gln134fs
Coding: c.399del
MANE Select: NM_001242
Type: Deletion
Location: chr12:6450303 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 5 PDB

Full CD27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lymphoproliferative syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to CD27 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

CD27 p.Asp52fs Pathogenic/Likely pathogenic ★★ same condition
CD27 p.Leu136fs Pathogenic/Likely pathogenic ★★ same condition
CD27 p.His86fs Pathogenic ★ same condition
CD27 p.Ser137fs Pathogenic ★ same condition
CD27 c.449-16_449-13del Likely benign ★ same condition
CD27 p.Cys53Tyr Pathogenic ★★ same condition
CD27 p.His80fs Pathogenic/Likely pathogenic ★★ same condition
CD27 p.Ala164Pro Uncertain significance ★★ ⚠ 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/cd27-p-gln134fs (accessed [today's date]).

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