Is ADA p.Glu337del (c.1008AGA[1]) pathogenic?

ADA p.Glu337del (c.1008AGA[1]) is classified Likely pathogenic in ADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency.

ADA p.Glu337del

Q: What condition is associated with ADA p.Glu337del (c.1008AGA[1])?

ADA p.Glu337del (c.1008AGA[1]) is associated with severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency, severe combined immunodeficiency (ClinVar).

Q: How is Severe combined immunodeficiency due to adenosine deaminase deficiency inherited?

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

c.1008AGA[1] · VCV3895923

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

Conditions

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

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 -2.7	GERP -3.1

Variant & gene context

Gene: ADA
Protein: p.Glu337del
Coding: c.1008AGA[1]
MANE Select: NM_000022
Type: Microsatellite
Location: chr20:44620364 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 337: an α-helix; a UniProt-annotated variant site (in adascid)

Full ADA 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-negative, due to adenosine deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency

For Severe combined immunodeficiency due to adenosine deaminase deficiency (Orphanet):

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

Similar variants

ADA p.Glu337Lys Uncertain significance ★★ ⚠ same residue
ADA p.Glu337Ter Pathogenic ★ same residue
ADA p.Glu337= Likely benign ★ same residue
ADA p.Arg341fs Pathogenic ★★ same condition
ADA c.362+5_362+8del Likely pathogenic ★ same condition
ADA c.33+6CG[3] Likely benign ★ same condition
ADA c.34-29CT[3] Likely benign ★ same condition
ADA c.96-17_96-14del Likely benign ★ 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/ada-p-glu337del (accessed [today's date]).

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