Is RAG2 p.Pro17Thr (c.48_49delinsAA) pathogenic?

RAG2 p.Pro17Thr (c.4849delinsAA) is classified Uncertain significance in RAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). Associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive.

RAG2 p.Pro17Thr

Q: What condition is associated with RAG2 p.Pro17Thr (c.48_49delinsAA)?

RAG2 p.Pro17Thr (c.48_49delinsAA) is associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, combined immunodeficiency with skin granulomas (ClinVar).

Q: How is Severe combined immunodeficiency due to complete RAG1/2 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.48_49delinsAA · VCV4793151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,580 bp · p 0.79 · regional, not allelic

Variant & gene context

Gene: RAG2
Protein: p.Pro17Thr
Coding: c.48_49delinsAA
MANE Select: NM_000536
Type: Indel
Location: chr11:36594120 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 75.98 · 1 PDB

Full RAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined immunodeficiency with skin granulomas

For Severe combined immunodeficiency due to complete RAG1/2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RAG2 p.Pro17= Likely benign ★ same residue
RAG2 p.Lys283fs Likely pathogenic ★ same condition
RAG2 p.Gly414Asn Uncertain significance ★ same condition
RAG2 p.His47Leu Uncertain significance ★ same condition
RAG2 p.Arg229Gln Pathogenic ★★★ ⚠ same condition
RAG2 p.Arg229Trp Pathogenic ★★★ ⚠ same condition
RAG2 p.Arg39Gly Pathogenic ★★★ ⚠ same condition
RAG2 p.Arg73Cys Likely pathogenic ★★★ ⚠ 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/rag2-p-pro17thr (accessed [today's date]).

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