Is CD27 p.Cys43= (c.129T>C) pathogenic?

CD27 p.Cys43= (c.129T>C) is classified Likely benign in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-22). Very rare (popmax 0.00134%, afr); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Cys43= (c.129T>C)?

CD27 p.Cys43= (c.129T>C) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Cys43= (c.129T>C) in the general population?

CD27 p.Cys43= (c.129T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

CD27 p.Cys43=

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.129T>C · rs1230032711 · VCV1915920

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, 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 -0.43	GERP -0.69
Overall
CADD	4.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,902 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000929% 15/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,004
African / African-Americangrpmax	0.00134%	74,902
South Asian	0.0011%	91,082
European (non-Finnish)	0.000932%	107,271

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys43=
Coding: c.129T>C
MANE Select: NM_001242
dbSNP: rs1230032711
Type: single nucleotide variant
Location: chr12:6445224 (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 43: a disulfide bond; an α-helix

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-cys43 (accessed [today's date]).

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