Is CD27 p.Arg78Gln (c.233G>A) pathogenic?

CD27 p.Arg78Gln (c.233G>A) is classified Uncertain significance in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-13). AlphaMissense: likely benign (0.166); Ultra-rare (popmax 0.0194%, nfe); Associated with lymphoproliferative syndrome 2.

What condition is associated with CD27 p.Arg78Gln (c.233G>A)?

CD27 p.Arg78Gln (c.233G>A) is associated with lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Arg78Gln (c.233G>A) in the general population?

CD27 p.Arg78Gln (c.233G>A) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

What do computational predictors say about CD27 p.Arg78Gln (c.233G>A)?

AlphaMissense predicts likely benign (score 0.166) — an in-silico prediction, not a clinical call.

CD27 p.Arg78Gln

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.233G>A · rs145433356 · VCV649825

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

lymphoproliferative syndrome 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.166	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	23.8	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 0.0194% European (non-Finnish) · 229/1,180,042 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0151% 243/1,613,766 alleles · ultra-rare exomes 228/1,461,632 · genomes 15/152,134 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,153
Finnishnot grpmax-eligible	0.00941%	10,631
Remaining individualsnot grpmax-eligible	0.008%	12,496
Admixed American	0.00333%	29,987
South Asian	0.0011%	91,092

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.Arg78Gln
Coding: c.233G>A
MANE Select: NM_001242
dbSNP: rs145433356
Type: single nucleotide variant
Location: chr12:6445520 (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-arg78gln (accessed [today's date]).

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