Is CD27 p.Trp8Ter (c.24G>A) pathogenic?

CD27 p.Trp8Ter (c.24G>A) is classified Pathogenic in CD27 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-03-01). Very rare (popmax 0.00111%, sas); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Trp8Ter (c.24G>A)?

CD27 p.Trp8Ter (c.24G>A) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Trp8Ter (c.24G>A) in the general population?

CD27 p.Trp8Ter (c.24G>A) is very rare (popmax 0.00111%, sas) (gnomAD).

CD27 p.Trp8Ter

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.24G>A · rs398122933 · VCV40889

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

lymphoproliferative syndrome 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.3	GERP 0.4, phastCons 1
Overall
CADD	36.0	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

Grpmax group 0.00111% South Asian · 1/89,974 alleles

Overall 0.000125% 2/1,606,410 alleles · very rare exomes 2/1,454,122 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	89,974
European (non-Finnish)	8.5e-05%	1,177,076

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: CD27
Protein: p.Trp8Ter
Coding: c.24G>A
MANE Select: NM_001242
dbSNP: rs398122933
Type: single nucleotide variant
Location: chr12:6445119 (GRCh38)

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

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-trp8ter (accessed [today's date]).

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