Is CD27 p.Ser70Pro (c.208T>C) pathogenic?

CD27 p.Ser70Pro (c.208T>C) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-26). AlphaMissense: likely pathogenic (0.9612); Ultra-rare (popmax 0.015%, amr); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Ser70Pro (c.208T>C)?

CD27 p.Ser70Pro (c.208T>C) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Ser70Pro (c.208T>C) in the general population?

CD27 p.Ser70Pro (c.208T>C) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CD27 p.Ser70Pro (c.208T>C)?

AlphaMissense predicts likely pathogenic (score 0.9612) — an in-silico prediction, not a clinical call.

CD27 p.Ser70Pro

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.208T>C · rs868070072 · VCV1508920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9612 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9612	likely pathogenic · top 2% in CD27
REVEL	0.626	indeterminate
SaProt	LLR -12.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.015% Admixed American · 9/59,992 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000682% 11/1,613,952 alleles · ultra-rare exomes 1/1,461,772 · genomes 10/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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.Ser70Pro
Coding: c.208T>C
MANE Select: NM_001242
dbSNP: rs868070072
Type: single nucleotide variant
Location: chr12:6445495 (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.Ser70= 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
CD27 p.Arg182Ser 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-ser70pro (accessed [today's date]).

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