Is CD27 p.Glu227= (c.681G>A) pathogenic?

CD27 p.Glu227= (c.681G>A) is classified Likely benign in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). Very rare (popmax 0.00935%, afr); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Glu227= (c.681G>A)?

CD27 p.Glu227= (c.681G>A) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Glu227= (c.681G>A) in the general population?

CD27 p.Glu227= (c.681G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

CD27 p.Glu227=

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.681G>A · rs1949541380 · VCV1124997

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.36	GERP -0.12
Overall
CADD	6.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,906 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,701
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Glu227=
Coding: c.681G>A
dbSNP: rs1949541380
Type: single nucleotide variant
Location: chr12:6451290 (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-glu227 (accessed [today's date]).

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