Is CD27 p.Phe210Leu (c.630C>A) pathogenic?

CD27 p.Phe210Leu (c.630C>A) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-29). AlphaMissense: likely pathogenic (0.6439); Very rare (popmax 8.47e-05%, nfe); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Phe210Leu (c.630C>A)?

CD27 p.Phe210Leu (c.630C>A) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Phe210Leu (c.630C>A) in the general population?

CD27 p.Phe210Leu (c.630C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD27 p.Phe210Leu (c.630C>A)?

AlphaMissense predicts likely pathogenic (score 0.6439) — an in-silico prediction, not a clinical call.

CD27 p.Phe210Leu

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.630C>A · VCV3663590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lymphoproliferative syndrome 2

Computational evidence

Protein change
AlphaMissense	0.6439	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.005	GERP -0.054, phastCons 0.002
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	14.83	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,986 alleles

Overall 6.84e-05% 1/1,461,844 alleles · very rare

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.Phe210Leu
Coding: c.630C>A
Type: single nucleotide variant
Location: chr12:6450986 (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-phe210leu (accessed [today's date]).

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