Is CD27 p.Cys84fs (c.250dup) pathogenic?

CD27 p.Cys84fs (c.250dup) is classified Pathogenic in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). Very rare (popmax 0.000508%, nfe); Associated with combined immunodeficiency.

What condition is associated with CD27 p.Cys84fs (c.250dup)?

CD27 p.Cys84fs (c.250dup) is associated with combined immunodeficiency, immunodeficiency disease (ClinVar).

How common is CD27 p.Cys84fs (c.250dup) in the general population?

CD27 p.Cys84fs (c.250dup) is very rare (popmax 0.000508%, nfe) (gnomAD).

CD27 p.Cys84fs

c.250dup · rs1592117677 · VCV827694

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

combined immunodeficiency

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,018 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,432 alleles · very rare

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.Cys84fs
Coding: c.250dup
MANE Select: NM_001242
dbSNP: rs1592117677
Type: Duplication
Location: chr12:6445536 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 5 PDB
Residue 84: a disulfide bond; an α-helix

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

Disease context

combined immunodeficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency disease

Similar variants

CD27 p.Arg107Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
CD27 p.His80fs Pathogenic/Likely pathogenic ★★ same type
CD27 c.136+11dup Benign ★ same type

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-cys84fs (accessed [today's date]).

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