Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: genes and variants
Explore variant evidence for Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome across 1 analyzed protein (SMAD4). Linked ClinVar records include 2 pathogenic or likely pathogenic variants, 39 variants of uncertain significance and 8 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. Counts refer to the selected disease label.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
SMAD4: SMAD family member 4
It forms transcriptional complexes with activated receptor-regulated SMADs and is the central nuclear mediator shared by TGF-beta and BMP pathways. Germline loss-of-function variants cause juvenile polyposis or combined juvenile-polyposis-HHT, while specific gain-of-function variants cause Myhre syndrome.
2 ClinVar pathogenic / likely pathogenic and 47 uncertain variants in SMAD4 have source records linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SMAD4 R361G | 361 | MH2 | Pathogenic / likely pathogenic (★★) |
| SMAD4 G386D | 386 | MH2 | Pathogenic / likely pathogenic |
Same protein, different disease
- Juvenile polyposis syndrome also has ClinVar records linked to SMAD4 variants; they fall mostly in different places as the Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome variants (18 pathogenic / likely pathogenic).
- Familial thoracic aortic aneurysm and aortic dissection also has ClinVar records linked to SMAD4 variants; they fall mostly in different places as the Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome variants (12 pathogenic / likely pathogenic).
Diseases related to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- Familial thoracic aortic aneurysm and aortic dissection, also linked to SMAD4
- Juvenile polyposis syndrome, also linked to SMAD4
- Esophageal cancer, also linked to SMAD4
- Familial pancreatic carcinoma, also linked to SMAD4
- Hereditary hemorrhagic telangiectasia, also linked to SMAD4
- Carcinoma of pancreas, also linked to SMAD4
- Generalized juvenile polyposis/juvenile polyposis coli, also linked to SMAD4
Frequently asked questions
Which genes have records linked to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome?
This view contains 1 analyzed proteins: SMAD4. 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 2 pathogenic or likely pathogenic variants, 39 variants of uncertain significance and 8 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 60 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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