Is CD27 p.Arg167= (c.501G>A) pathogenic?

CD27 p.Arg167= (c.501G>A) is classified Likely benign in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Rare (popmax 0.104%, afr); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Arg167= (c.501G>A)?

CD27 p.Arg167= (c.501G>A) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Arg167= (c.501G>A) in the general population?

CD27 p.Arg167= (c.501G>A) is rare (popmax 0.104%, afr) (gnomAD).

CD27 p.Arg167=

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.501G>A · rs143249431 · VCV1137740

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.104%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.99, phastCons 0.089
Overall
CADD	8.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% African / African-American · 78/75,060 alleles

Filtering AF 0.0853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0785%

Overall 0.00546% 88/1,613,142 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	962
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0032%	31,248

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.Arg167=
Coding: c.501G>A
MANE Select: NM_001242
dbSNP: rs143249431
Type: single nucleotide variant
Location: chr12:6450593 (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.Cys53Tyr Pathogenic ★★ same condition
CD27 p.Ala164Pro Uncertain significance ★★ ⚠ same condition
CD27 p.Ala229Thr Uncertain significance ★★ ⚠ same condition
CD27 p.Arg155Thr Uncertain significance ★★ ⚠ same condition
CD27 p.Arg172Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Arg172Gly Uncertain significance ★★ ⚠ same condition
CD27 p.Arg182Ser Uncertain significance ★★ ⚠ same condition
CD27 p.Arg238Lys 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-arg167 (accessed [today's date]).

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