SMAD4 (SMAD family member 4) variants and mutations
SMAD4 (also known as SMAD family member 4) is a human protein-coding gene encoding a SMAD family member 4 protein. 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. This analysis covers 2,847 SMAD4 variants and mutations. Of these, 38% have computational variant effect predictions. Disease context includes juvenile polyposis syndrome, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, and Myhre syndrome. Example SMAD4 variants include M1?, M1I, and M1T.
Variant analysis overview
- Gene: SMAD4
- Protein: SMAD family member 4
- UniProt accession: Q13485
- Organism: Homo sapiens
- Variants analyzed: 2847
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,700 unspecified-consequence records; 22 missense variants; 113 synonymous variants; 4 frameshift variants; 2 in-frame insertions; 2 splice-region variants; 1 in-frame deletions; 3 substitution
- Prediction scores: 1,084 variants have prediction scores (38% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: juvenile polyposis syndrome, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Myhre syndrome, generalized juvenile polyposis/juvenile polyposis coli, familial pancreatic carcinoma, familial thoracic aortic aneurysm and aortic dissection, colorectal adenocarcinoma, pancreatic adenocarcinoma, hereditary hemorrhagic telangiectasia, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, gastric adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 4 binding sites; 3 post-translational modification sites.
- Structural context: 1,773 variants have structural context.
- PTM context: 16 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable SMAD4 variants
Examples include M1?, M1I, M1T, M1V, D2A, D2E, D2H, D2N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10074, Variant assessed as somatic; high impact.
- M1I (p.Met1Ile), rs973470216, ClinGen CA300080946, ClinVar RCV001204996, ClinGen CA402457192, MetaLR 0.79, MetaSVM 0.03, Uncertain significance, Juvenile polyposis syndrome
- M1T (p.Met1Thr), rs1372924000, ClinGen CA402457190, ClinVar RCV002599165, ClinVar RCV004560050, MetaLR 0.81, MetaSVM 0.28, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- M1V (p.Met1Val), rs1064795777, ClinGen CA16620697, ClinVar RCV000481044, ClinVar RCV001865469, MetaLR 0.80, MetaSVM 0.24, Uncertain significance, Juvenile polyposis syndrome; not provided; Juvenile polyposis/hereditary hemorrh
- D2A (p.Asp2Ala), rs2144400144, ClinGen CA402457197, ClinVar RCV003761730, ClinVar RCV004011651, AlphaMissense 0.27, MetaLR 0.74, Uncertain significance, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Juvenile poly
- D2E (p.Asp2Glu), Ensembl rs2144400152, Likely benign
- D2H (p.Asp2His), rs1555684979, ClinGen CA402457195, ClinVar RCV003021179, Ensembl rs1555684979, AlphaMissense 0.09, MetaLR 0.76, Uncertain significance, Juvenile polyposis syndrome
- D2N (p.Asp2Asn), rs1555684979, ClinGen CA402457194, ClinVar RCV002317321, ClinVar RCV006556282, REVEL 0.33, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- D2V (p.Asp2Val), Ensembl rs2144400144
- D2Y (p.Asp2Tyr), Ensembl rs1555684979, Uncertain significance
- D2G (p.Asp2Gly), gnomAD 18-51047051-A-G, REVEL 0.31, CADD 22.50
- N3D (p.Asn3Asp), cosmic curated COSV61686, ExAC rs774342820, gnomAD rs774342820, REVEL 0.28, CADD 21.00
- N3I (p.Asn3Ile), Ensembl rs757702252, Uncertain significance
- N3K (p.Asn3Lys), ExAC rs762273127, TOPMed rs762273127, gnomAD rs762273127, Likely benign
- N3S (p.Asn3Ser), rs757702252, ClinGen CA300080951, ClinVar RCV002233409, ClinVar RCV002274093, REVEL 0.29, CADD 15.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- N3Y (p.Asn3Tyr), ExAC rs774342820, gnomAD rs774342820, REVEL 0.29, CADD 23.50
- N3N (p.Asn3Asn), rs762273127, gnomAD 18-51047055-T-C, CADD 12.00
- M4I (p.Met4Ile), Ensembl rs2144400205
- M4K (p.Met4Lys), Ensembl rs2144400196, Uncertain significance
- M4L (p.Met4Leu), cosmic curated COSV10074, Ensembl rs2144400190
- M4R (p.Met4Arg), Ensembl rs2144400196, Uncertain significance
- M4T (p.Met4Thr), rs2144400196, ClinGen CA402457213, ClinVar RCV001907861, Ensembl rs2144400196, AlphaMissense 0.14, MetaLR 0.93, Uncertain significance, Juvenile polyposis syndrome
- M4V (p.Met4Val), cosmic curated COSV10886
- S5A (p.Ser5Ala), Ensembl rs2144400212
- S5C (p.Ser5Cys), rs2144400216, ClinGen CA402457221, cosmic curated COSV61688, ClinVar RCV002389893, AlphaMissense 0.24, MetaLR 0.95, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- S5F (p.Ser5Phe), Ensembl rs2144400216, Uncertain significance
- S5P (p.Ser5Pro), Ensembl rs2144400212
- S5T (p.Ser5Thr), Ensembl rs2144400212
- S5Y (p.Ser5Tyr), Ensembl rs2144400216, Uncertain significance
- I6F (p.Ile6Phe), gnomAD rs1376500870, Uncertain significance
- I6L (p.Ile6Leu), gnomAD rs1376500870, Uncertain significance
- I6N (p.Ile6Asn), Ensembl rs1599181007, Uncertain significance
- I6S (p.Ile6Ser), Ensembl rs1599181007, Uncertain significance
- I6T (p.Ile6Thr), rs1599181007, ClinGen CA402457233, ClinVar RCV001013227, ClinVar RCV002319177, AlphaMissense 0.09, MetaLR 0.67, Uncertain significance, Juvenile polyposis syndrome; Hereditary cancer-predisposing syndrome; not provid
- I6V (p.Ile6Val), rs1376500870, ClinGen CA402457227, cosmic curated COSV61692, ClinVar RCV000569854, REVEL 0.33, CADD 16.10, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- T7* (p.Thr7Ter), cosmic curated COSV61690
- T7A (p.Thr7Ala), Ensembl rs2144400256, REVEL 0.34, CADD 22.00
- T7K (p.Thr7Lys), 1000Genomes rs372316981, ESP rs372316981, ExAC rs372316981, TOPMed rs372316981, Benign
- T7M (p.Thr7Met), rs372316981, ClinGen CA186263, ClinVar RCV000162438, ClinVar RCV000196213, REVEL 0.44, AlphaMissense 0.13, Conflicting interpretations, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Juvenile poly
- T7P (p.Thr7Pro), Ensembl rs2144400256
- T7R (p.Thr7Arg), rs372316981, ClinGen CA402457247, ClinVar RCV001237501, 1000Genomes rs372316981, AlphaMissense 0.13, MetaLR 0.89, Uncertain significance, Juvenile polyposis syndrome
- T7S (p.Thr7Ser), Ensembl rs2144400256
- T7T (p.Thr7Thr), rs142292491, gnomAD 18-51047067-G-T, CADD 1.41
- N8I (p.Asn8Ile), Ensembl rs876658568, Uncertain significance
- N8K (p.Asn8Lys), TOPMed rs1909566006, Likely benign
- N8S (p.Asn8Ser), rs876658568, ClinGen CA10580969, ClinVar RCV002229220, ClinVar RCV002310804, REVEL 0.34, CADD 19.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- N8Y (p.Asn8Tyr), Ensembl rs2144400281
- T9A (p.Thr9Ala), rs2144400315, ClinGen CA402457267, ClinVar RCV001995772, ClinVar RCV002425375, AlphaMissense 0.09, MetaLR 0.76, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- T9I (p.Thr9Ile), rs1555684986, ClinGen CA402457275, ClinVar RCV002231712, ClinVar RCV003584649, AlphaMissense 0.15, MetaLR 0.81, Uncertain significance, Juvenile polyposis syndrome; Familial thoracic aortic aneurysm and aortic dissec
- T9K (p.Thr9Lys), Ensembl rs1555684986, Uncertain significance
- T9P (p.Thr9Pro), rs2144400315, ClinGen CA402457265, ClinVar RCV002426217, Ensembl rs2144400315, REVEL 0.39, AlphaMissense 0.09, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- T9R (p.Thr9Arg), Ensembl rs1555684986, Uncertain significance
- T9S (p.Thr9Ser), Ensembl rs2144400315, Uncertain significance
- P10A (p.Pro10Ala), Ensembl rs2144400339, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- P10L (p.Pro10Leu), rs1909566256, ClinGen CA402457286, cosmic curated COSV10465, ClinVar RCV001224928, AlphaMissense 0.68, MetaLR 0.91, Uncertain significance, not provided; Juvenile polyposis syndrome
- P10Q (p.Pro10Gln), Ensembl rs1909566256, Uncertain significance
- P10R (p.Pro10Arg), Ensembl rs1909566256, Uncertain significance
- P10S (p.Pro10Ser), rs2144400339, ClinGen CA402457281, ClinVar RCV002438047, Ensembl rs2144400339, AlphaMissense 0.61, MetaLR 0.92, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- P10T (p.Pro10Thr), Ensembl rs2144400339, Uncertain significance
- P10P (p.Pro10Pro), rs761044209, gnomAD 18-51047076-A-T, CADD 9.34
- T11A (p.Thr11Ala), rs587780791, ClinGen CA332845, ClinVar RCV000123262, ClinVar RCV005055593, AlphaMissense 0.07, MetaLR 0.92, Uncertain significance, Juvenile polyposis syndrome
- T11I (p.Thr11Ile), Ensembl rs2144400374
- T11K (p.Thr11Lys), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10074, Ensembl rs2144400374, Variant assessed as somatic; moderate impact.
- T11P (p.Thr11Pro), rs587780791, ClinGen CA402457291, ClinVar RCV003474041, Ensembl rs587780791, AlphaMissense 0.07, MetaLR 0.92, Uncertain significance, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- T11R (p.Thr11Arg), Ensembl rs2144400374
- T11S (p.Thr11Ser), rs587780791, ClinGen CA402457288, ClinVar RCV001192752, Ensembl rs587780791, AlphaMissense 0.07, MetaLR 0.92, Uncertain significance, not specified
- S12C (p.Ser12Cys), Ensembl rs2144400400
- S12G (p.Ser12Gly), cosmic curated COSV10465
- S12I (p.Ser12Ile), Ensembl rs2144400408, Uncertain significance
- S12N (p.Ser12Asn), rs2144400408, ClinGen CA402457305, ClinVar RCV001899152, Ensembl rs2144400408, AlphaMissense 0.79, MetaLR 0.93, Uncertain significance, Juvenile polyposis syndrome
- S12R (p.Ser12Arg), Ensembl rs2144400421, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S12T (p.Ser12Thr), Ensembl rs2144400408, Uncertain significance
- N13D (p.Asn13Asp), rs1909566487, ClinGen CA402457317, ClinVar RCV001236702, ClinVar RCV005403002, AlphaMissense 0.43, MetaLR 0.93, Uncertain significance, Hereditary cancer-predisposing syndrome; Juvenile polyposis syndrome
- N13I (p.Asn13Ile), ExAC rs281875323, TOPMed rs281875323, gnomAD rs281875323, Likely benign
- N13K (p.Asn13Lys), ESP rs376371717, ExAC rs376371717, TOPMed rs376371717, gnomAD rs376371717, Likely benign
- N13S (p.Asn13Ser), rs281875323, ClinGen CA162125, ClinVar RCV000059736, ClinVar RCV000122056, REVEL 0.41, CADD 22.40, Conflicting interpretations, Juvenile polyposis syndrome; Hereditary cancer-predisposing syndrome; Familial t
- N13Y (p.Asn13Tyr), Ensembl rs1909566487, Uncertain significance
- N13N (p.Asn13Asn), rs376371717, gnomAD 18-51047085-T-C, CADD 10.50
- D14E (p.Asp14Glu), Ensembl rs2144400462
- D14H (p.Asp14His), Ensembl rs2144400451
- D14N (p.Asp14Asn), Ensembl rs2144400451
- D14V (p.Asp14Val), Ensembl rs2144400459
- D14Y (p.Asp14Tyr), Ensembl rs2144400451
- A15D (p.Ala15Asp), cosmic curated COSV10817, Ensembl rs2144400485, Uncertain significance
- A15G (p.Ala15Gly), Ensembl rs2144400485, Uncertain significance
- A15P (p.Ala15Pro), TOPMed rs1909566748, gnomAD rs1909566748, Uncertain significance
- A15S (p.Ala15Ser), rs1909566748, ClinGen CA402457349, ClinVar RCV003764360, ClinVar RCV006292460, AlphaMissense 0.86, MetaLR 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- A15T (p.Ala15Thr), rs1909566748, ClinGen CA402457346, cosmic curated COSV61694, ClinVar RCV001360486, REVEL 0.68, AlphaMissense 0.86, Uncertain significance, Juvenile polyposis syndrome
- A15V (p.Ala15Val), rs2144400485, ClinGen CA402457354, cosmic curated COSV61684, ClinVar RCV002975984, REVEL 0.69, CADD 25.80, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- C16* (p.Cys16Ter), Ensembl rs2144400522
- C16F (p.Cys16Phe), rs1555684993, ClinGen CA402457376, ClinVar RCV001867171, Ensembl rs1555684993, AlphaMissense 0.98, MetaLR 0.96, Uncertain significance, Juvenile polyposis syndrome
- C16S (p.Cys16Ser), Ensembl rs2144400500, REVEL 0.85, AlphaMissense 0.98, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- C16W (p.Cys16Trp), Ensembl rs2144400522
- C16Y (p.Cys16Tyr), rs1555684993, ClinGen CA402457373, ClinVar RCV001051762, ClinVar RCV004559871, AlphaMissense 0.98, MetaLR 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- C16C (p.Cys16Cys), rs2144400522, gnomAD 18-51047094-T-C, CADD 11.60
- L17M (p.Leu17Met), Ensembl rs1555684997, Likely benign
- L17Q (p.Leu17Gln), Ensembl rs2144400546
- L17V (p.Leu17Val), Ensembl rs1555684997, Likely benign
- L17L (p.Leu17Leu), rs1555684997, gnomAD 18-51047095-C-T, CADD 10.70
- S18C (p.Ser18Cys), Ensembl rs2144400562
- S18I (p.Ser18Ile), Ensembl rs2144400567
- S18N (p.Ser18Asn), Ensembl rs2144400567, Uncertain significance, Juvenile polyposis syndrome
- S18R (p.Ser18Arg), gnomAD rs1599181066, Likely benign
- S18T (p.Ser18Thr), Ensembl rs2144400567, REVEL 0.51, CADD 24.20
- S18S (p.Ser18Ser), rs1599181066, gnomAD 18-51047100-C-T, CADD 13.00
- I19F (p.Ile19Phe), Ensembl rs1568202964, Uncertain significance
- I19M (p.Ile19Met), rs754401427, ClinGen CA402457421, ClinVar RCV002359882, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- I19N (p.Ile19Asn), Ensembl rs2144400593
- I19S (p.Ile19Ser), Ensembl rs2144400593
- I19V (p.Ile19Val), rs1568202964, ClinGen CA402457410, ClinVar RCV000774816, ClinVar RCV001873150, AlphaMissense 0.99, MetaLR 0.52, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- V20L (p.Val20Leu), rs1568202971, ClinGen CA402457426, ClinVar RCV000777148, Ensembl rs1568202971, AlphaMissense 0.98, MetaLR 0.59, Uncertain significance, Hereditary cancer-predisposing syndrome
- V20M (p.Val20Met), Ensembl rs1568202971, Uncertain significance
- V20V (p.Val20Val), rs1057520442, gnomAD 18-51047106-G-A, CADD 6.92
- H21D (p.His21Asp), Ensembl rs2144400625
- H21L (p.His21Leu), gnomAD rs1280706054, Uncertain significance
- H21N (p.His21Asn), Ensembl rs2144400625
- H21Q (p.His21Gln), Ensembl rs1555685004, Likely benign
- H21R (p.His21Arg), rs1280706054, ClinGen CA402457444, ClinVar RCV002311919, ClinVar RCV002528944, REVEL 0.64, CADD 25.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- H21Y (p.His21Tyr), Ensembl rs2144400625
- H21H (p.His21His), rs1555685004, gnomAD 18-51047109-T-C, CADD 11.40
- S22C (p.Ser22Cys), Ensembl rs2144400650
- S22I (p.Ser22Ile), Ensembl rs2144400654
- S22R (p.Ser22Arg), Ensembl rs2144400660
- S22S (p.Ser22Ser), gnomAD 18-51047112-T-C, CADD 13.30
- L23* (p.Leu23Ter), Ensembl rs2144400677
- L23F (p.Leu23Phe), Ensembl rs2144400683, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- L23M (p.Leu23Met), Ensembl rs2144400672
- L23W (p.Leu23Trp), cosmic curated COSV61685
- M24I (p.Met24Ile), rs2144400716, Ensembl rs2144400716, ClinGen CA402457492, ClinVar RCV003585811, AlphaMissense 0.98, MetaLR 0.52, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- M24L (p.Met24Leu), gnomAD rs876659391, Uncertain significance
- M24R (p.Met24Arg), Ensembl rs2144400707
- M24V (p.Met24Val), rs876659391, ClinGen CA10580970, ClinVar RCV000214905, ClinVar RCV000547868, REVEL 0.58, CADD 24.80, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- C25* (p.Cys25Ter), Ensembl rs1555685008, Likely benign
- C25G (p.Cys25Gly), Ensembl rs2144400721
- C25S (p.Cys25Ser), Ensembl rs2144400721
- C25W (p.Cys25Trp), Ensembl rs1555685008, Likely benign
- C25Y (p.Cys25Tyr), NCI-TCGA Cosmic COSV6168, cosmic curated COSV61689, Variant assessed as somatic; moderate impact.
- C25F (p.Cys25Phe), gnomAD 18-51047120-G-T, REVEL 0.65, CADD 28.10
- H26D (p.His26Asp), Ensembl rs2144400736, Uncertain significance
- H26L (p.His26Leu), Ensembl rs2144400741
- H26N (p.His26Asn), Ensembl rs2144400736, Uncertain significance
- H26Q (p.His26Gln), Ensembl rs2144400751
- H26R (p.His26Arg), rs2144400741, ClinGen CA402457523, ClinVar RCV002409895, AlphaMissense 0.92, MetaLR 0.36, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- H26Y (p.His26Tyr), rs2144400736, ClinGen CA402457517, ClinVar RCV001867537, Ensembl rs2144400736, AlphaMissense 0.96, MetaLR 0.46, Uncertain significance, Juvenile polyposis syndrome
- R27* (p.Arg27Ter), Ensembl rs2144400756
- R27G (p.Arg27Gly), rs2144400756, ClinGen CA402457529, ClinVar RCV003597045, ClinVar RCV005030132, Uncertain significance, Juvenile polyposis syndrome; Familial thoracic aortic aneurysm and aortic dissec
- R27K (p.Arg27Lys), Ensembl rs2144400769
- R27S (p.Arg27Ser), Ensembl rs2144400776
- R27T (p.Arg27Thr), Ensembl rs2144400769
- Q28* (p.Gln28Ter), Ensembl rs2144400785, Uncertain significance
- Q28E (p.Gln28Glu), Ensembl rs2144400785, Uncertain significance
- Q28H (p.Gln28His), ExAC rs778465458, TOPMed rs778465458, gnomAD rs778465458, Benign
- Q28K (p.Gln28Lys), rs2144400785, ClinGen CA402457539, ClinVar RCV002033178, Ensembl rs2144400785, AlphaMissense 0.50, MetaLR 0.53, Uncertain significance, Juvenile polyposis syndrome
- Q28L (p.Gln28Leu), Ensembl rs1599181096, Uncertain significance
- Q28R (p.Gln28Arg), rs1599181096, ClinGen CA402457548, ClinVar RCV002337071, Ensembl rs1599181096, REVEL 0.54, CADD 26.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- Q28Q (p.Gln28Gln), rs778465458, gnomAD 18-51047130-A-G, CADD 12.70
- G29A (p.Gly29Ala), Ensembl rs2144400817, Uncertain significance
- G29C (p.Gly29Cys), Ensembl rs2144400809
- G29D (p.Gly29Asp), rs2144400817, ClinGen CA402457561, ClinVar RCV003596373, ClinVar RCV004775422, AlphaMissense 0.62, MetaLR 0.53, Uncertain significance, Juvenile polyposis syndrome; not provided
- G29R (p.Gly29Arg), Ensembl rs2144400809, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial thoracic aortic aneurysm and a
- G29S (p.Gly29Ser), Ensembl rs2144400809
- G29V (p.Gly29Val), Ensembl rs2144400817, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predi
- G29G (p.Gly29Gly), gnomAD 18-51047133-T-C, CADD 11.40
- G30* (p.Gly30Ter), cosmic curated COSV61684
- G30A (p.Gly30Ala), Ensembl rs2144400831, Uncertain significance
- G30E (p.Gly30Glu), Ensembl rs2144400831, Uncertain significance
- G30V (p.Gly30Val), rs2144400831, ClinGen CA402457576, ClinVar RCV003597022, Ensembl rs2144400831, AlphaMissense 0.85, MetaLR 0.47, Uncertain significance, Juvenile polyposis syndrome
- E31D (p.Glu31Asp), Ensembl rs2144400863
- E31K (p.Glu31Lys), rs1909568048, ClinGen CA402457586, cosmic curated COSV61688, ClinVar RCV001185676, AlphaMissense 0.88, MetaLR 0.51, Uncertain significance, Hereditary cancer-predisposing syndrome
- E31Q (p.Glu31Gln), rs1909568048, ClinGen CA402457581, ClinVar RCV004015491, Ensembl rs1909568048, AlphaMissense 0.88, MetaLR 0.51, Uncertain significance, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- E31V (p.Glu31Val), Ensembl rs2144400856
- E31G (p.Glu31Gly), gnomAD 18-51047138-A-G, REVEL 0.60, CADD 29.30
- S32* (p.Ser32Ter), cosmic curated COSV61685
- S32I (p.Ser32Ile), Ensembl rs2144400871
- S32N (p.Ser32Asn), Ensembl rs2144400871
- S32R (p.Ser32Arg), cosmic curated COSV10967, Ensembl rs2144400882, Likely benign
- S32T (p.Ser32Thr), NCI-TCGA TCGA novel, Ensembl rs2144400871, Variant assessed as somatic; moderate impact.
- E33* (p.Glu33Ter), NCI-TCGA Cosmic COSV6168, NCI-TCGA Cosmic COSV6169, cosmic curated COSV61695, Variant assessed as somatic; high impact.
- E33A (p.Glu33Ala), Ensembl rs2144400896
- E33D (p.Glu33Asp), Ensembl rs2144400902
Public SMAD4 analysis runs
- SMAD4 analysis run — SMAD4 (2,847 variants) — completed 2026-08-18