Is CD27 p.Arg94Cys (c.280C>T) pathogenic?

CD27 p.Arg94Cys (c.280C>T) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-09). AlphaMissense: likely benign (0.2859); Very rare (popmax 0.00333%, amr); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Arg94Cys (c.280C>T)?

CD27 p.Arg94Cys (c.280C>T) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Arg94Cys (c.280C>T) in the general population?

CD27 p.Arg94Cys (c.280C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CD27 p.Arg94Cys (c.280C>T)?

AlphaMissense predicts likely benign (score 0.2859) — an in-silico prediction, not a clinical call.

CD27 p.Arg94Cys

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.280C>T · VCV3695917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
AlphaMissense	0.2859	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -13.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP -0.081, phastCons 0.5
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00124% 20/1,612,286 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
African / African-American	0.00267%	37,509
East Asian	0.00223%	44,876
South Asian	0.0022%	45,531
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00102%	98,322

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.Arg94Cys
Coding: c.280C>T
Type: single nucleotide variant
Location: chr12:6450184 (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-arg94cys (accessed [today's date]).

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