Is CD27 p.Pro260Leu (c.779C>T) pathogenic?

CD27 p.Pro260Leu (c.779C>T) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.1072); Very rare (popmax 0.00891%, eas); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Pro260Leu (c.779C>T)?

CD27 p.Pro260Leu (c.779C>T) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Pro260Leu (c.779C>T) in the general population?

CD27 p.Pro260Leu (c.779C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CD27 p.Pro260Leu (c.779C>T)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

CD27 p.Pro260Leu

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.779C>T · VCV3680462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -1.9
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	17.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000685% 10/1,460,434 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.00481%	20,801
South Asian	0.0022%	45,510
African / African-American	0.00133%	75,024

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.Pro260Leu
Coding: c.779C>T
MANE Select: NM_001242
Type: single nucleotide variant
Location: chr12:6451388 (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 260: the 'disordered' region

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.Pro260Arg Uncertain significance ★ ⚠ same residue
CD27 p.Pro260= Likely benign ★ same residue
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

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-pro260leu (accessed [today's date]).

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