Hereditary pulmonary alveolar proteinosis: genes and variants
Explore variant evidence for Hereditary pulmonary alveolar proteinosis across 3 analyzed proteins (ABCA3, SFTPC, SFTPB). Linked ClinVar records include 19 pathogenic or likely pathogenic variants, 343 variants of uncertain significance and 62 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Hereditary pulmonary alveolar proteinosis
ABCA3: Phospholipid-transporting ATPase ABCA3
It transports phospholipids into lamellar bodies of alveolar type II cells, supporting pulmonary surfactant assembly and normal gas exchange. Biallelic loss-of-function variants can cause neonatal respiratory failure or childhood interstitial lung disease.
12 ClinVar pathogenic / likely pathogenic and 311 uncertain variants in ABCA3 have source records linked to Hereditary pulmonary alveolar proteinosis. Association strength is not clinical gene validity.
SFTPC: Surfactant protein C
It contributes to pulmonary surfactant organization and is produced specifically by alveolar type II cells. Dominant pathogenic variants can cause interstitial lung disease across infancy and adulthood, often through protein misfolding and toxic cellular stress.
4 ClinVar pathogenic / likely pathogenic and 27 uncertain variants in SFTPC have source records linked to Hereditary pulmonary alveolar proteinosis. Association strength is not clinical gene validity.
SFTPB: Pulmonary surfactant-associated protein B
It lowers surface tension and stabilizes pulmonary surfactant films during repeated breathing cycles, preventing alveolar collapse at end expiration. Biallelic loss-of-function variants cause severe neonatal surfactant dysfunction and respiratory failure.
3 ClinVar pathogenic / likely pathogenic and 67 uncertain variants in SFTPB have source records linked to Hereditary pulmonary alveolar proteinosis. Association strength is not clinical gene validity.
Where Hereditary pulmonary alveolar proteinosis variants cluster
- ABCA3 ABC transporter 2 (positions 1381–1614): 4 of 12 ClinVar pathogenic / likely pathogenic variants, 2.4× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Hereditary pulmonary alveolar proteinosis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCA3 R43C | 43 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 R43H | 43 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 E1540K | 1540 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCA3 E292V | 292 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 R1550W | 1550 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCA3 P246L | 246 | Pathogenic / likely pathogenic (★★) | |
| SFTPC L110P | 110 | BRICHOS | Pathogenic / likely pathogenic (★★) |
| ABCA3 P147L | 147 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 P186L | 186 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 P248L | 248 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 V1399M | 1399 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| ABCA3 G1459D | 1459 | ABC transporter 2 | Pathogenic / likely pathogenic (★★) |
| SFTPC I73T | 73 | Pathogenic / likely pathogenic (★★) | |
| ABCA3 F1077I | 1077 | Pathogenic / likely pathogenic (★★) | |
| SFTPB C302G | 302 | Saposin B-type 3 | Pathogenic / likely pathogenic (★) |
| SFTPC Y113H | 113 | BRICHOS | Pathogenic / likely pathogenic (★) |
| SFTPC A112P | 112 | BRICHOS | Pathogenic / likely pathogenic (★) |
| SFTPB R252C | 252 | Saposin B-type 2 | Pathogenic / likely pathogenic (★) |
| SFTPB G244S | 244 | Saposin B-type 2 | Pathogenic / likely pathogenic (★) |
Which prediction tools work for Hereditary pulmonary alveolar proteinosis
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MetaLR: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 97 out of 100
- REVEL: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 94 out of 100
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
Same protein, different disease
- Interstitial lung disease due to ABCA3 deficiency also has ClinVar records linked to ABCA3 variants; they fall mostly in different places as the Hereditary pulmonary alveolar proteinosis variants (30 pathogenic / likely pathogenic).
- Neonatal acute respiratory distress with surfactant metabolism deficiency also has ClinVar records linked to SFTPC variants; they fall mostly in different places as the Hereditary pulmonary alveolar proteinosis variants (7 pathogenic / likely pathogenic).
Diseases related to Hereditary pulmonary alveolar proteinosis
- Neonatal acute respiratory distress with surfactant metabolism deficiency, also linked to ABCA3, SFTPB and SFTPC
- Interstitial lung disease, also linked to ABCA3 and SFTPC
- Marfan syndrome, also linked to ABCA3
- Interstitial lung disease due to ABCA3 deficiency, also linked to ABCA3
- Idiopathic pulmonary fibrosis, also linked to SFTPC
Frequently asked questions
Which genes have records linked to Hereditary pulmonary alveolar proteinosis?
This view contains 3 analyzed proteins: ABCA3, SFTPC, SFTPB. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 19 pathogenic or likely pathogenic variants, 343 variants of uncertain significance and 62 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 520 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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