Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency: genes and variants
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency is linked to 1 analyzed protein (ADA). 44 DNA variants are known to cause it; 118 more are uncertain, and 6 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
ADA: Adenosine deaminase
It degrades adenosine and deoxyadenosine, preventing accumulation of metabolites that are particularly toxic to developing lymphocytes. Biallelic deficiency causes severe combined immunodeficiency, while partial deficiency can present later with immune dysfunction.
44 disease-causing and 118 uncertain variants in ADA are linked to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency.
Known disease-causing variants in Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ADA R211H | 211 | Disease-causing (★★★) | |
| ADA R211C | 211 | Disease-causing (★★★) | |
| ADA R235W | 235 | Disease-causing (★★★) | |
| ADA S291L | 291 | Disease-causing (★★★) | |
| ADA P104L | 104 | Disease-causing (★★★) | |
| ADA G239D | 239 | Disease-causing (★★★) | |
| ADA P297L | 297 | Disease-causing (★★★) | |
| ADA R149W | 149 | Disease-causing (★★★) | |
| ADA G216R | 216 | Disease-causing (★★★) | |
| ADA L304R | 304 | Disease-causing (★★★) | |
| ADA R282Q | 282 | Disease-causing (★★★) | |
| ADA A329V | 329 | Disease-causing (★★★) | |
| ADA R101L | 101 | Disease-causing (★★) | |
| ADA V129M | 129 | Required for binding to DDP4 | Disease-causing (★★) |
| ADA R156L | 156 | Disease-causing (★★) | |
| ADA R156S | 156 | Disease-causing (★★) | |
| ADA H15D | 15 | Disease-causing (★★) | |
| ADA G74V | 74 | Disease-causing (★★) | |
| ADA R101Q | 101 | Disease-causing (★★) | |
| ADA R101W | 101 | Disease-causing (★★) | |
| ADA R156P | 156 | Disease-causing (★★) | |
| ADA R156H | 156 | Disease-causing (★★) | |
| ADA R156C | 156 | Disease-causing (★★) | |
| ADA R235Q | 235 | Disease-causing (★★) | |
| ADA H15L | 15 | Disease-causing (★★) | |
| ADA P126Q | 126 | Required for binding to DDP4 | Disease-causing (★★) |
| ADA V177M | 177 | Disease-causing (★★) | |
| ADA S291W | 291 | Disease-causing (★★) | |
| ADA G20R | 20 | Disease-causing (★★) | |
| ADA L107P | 107 | Disease-causing (★★) | |
| ADA R282L | 282 | Disease-causing (★★) | |
| ADA A83T | 83 | Disease-causing (★★) | |
| ADA A179D | 179 | Disease-causing (★★) | |
| ADA M1V | 1 | Disease-causing (★★) | |
| ADA H15P | 15 | Disease-causing (★) | |
| ADA R101G | 101 | Disease-causing (★) | |
| ADA V129L | 129 | Required for binding to DDP4 | Disease-causing (★) |
| ADA G74C | 74 | Disease-causing (★) | |
| ADA G74D | 74 | Disease-causing (★) | |
| ADA C154R | 154 | Disease-causing (★) | |
| ADA R211S | 211 | Disease-causing (★) | |
| ADA L106V | 106 | Disease-causing (★) | |
| ADA L152P | 152 | Disease-causing (★) | |
| ADA Y97C | 97 | Disease-causing |
Uncertain variants in Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ADA R149L | 149 | Uncertain (★) | +7: 2 other pathogenic changes within 3 positions; R149W at the same position is pathogenic; seen in 7e-07 of gnomAD DNA copies; REVEL 0.958 | |
| ADA P297Q | 297 | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (1R); P297L at the same position is pathogenic; REVEL 0.949 | |
| ADA R282W | 282 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R282L at the same position is pathogenic; REVEL 0.824 | |
| ADA G239S | 239 | Uncertain (★★★) | +6: in a 3D region that tolerates change poorly (2R); G239D at the same position is pathogenic; REVEL 0.972 | |
| ADA R149Q | 149 | Uncertain (★★★) | +6: 2 other pathogenic changes within 3 positions; R149W at the same position is pathogenic; REVEL 0.889 | |
| ADA L152M | 152 | Uncertain (★★★) | +6: 3 other pathogenic changes within 3 positions; L152P at the same position is pathogenic; REVEL 0.820 |
Which prediction tools work for Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 100 out of 100
- REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 95 out of 100
- SIFT: 95 out of 100
Diseases related to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
- Severe combined immunodeficiency disease, also linked to ADA
Frequently asked questions
Which genes are linked to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency?
In CATVariant, Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency is linked to 1 analyzed protein: ADA (Adenosine deaminase).
How many genetic variants are linked to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency?
202 variants: 44 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 118 are of uncertain significance or have conflicting reports.
Which uncertain variants in Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency look disease-causing?
6 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ADA R149L, ADA P297Q, ADA R282W, ADA G239S and ADA R149Q. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 36 disease-causing and 8 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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