CDH1 (Cadherin-1) variants and mutations
CDH1 (also known as Cadherin-1) is a human protein-coding gene encoding a cadherin-1 protein. Its E-cadherin-mediated adhesion preserves epithelial architecture and suppresses inappropriate cell detachment and invasion. Germline loss-of-function variants cause hereditary diffuse gastric cancer syndrome and substantially increase diffuse gastric and lobular breast-cancer risk. This analysis covers 4,399 CDH1 variants and mutations. Of these, 33% have computational variant effect predictions. Disease context includes developmental and epileptic encephalopathy 109, neurodegenerative disease, and undetermined early-onset epileptic encephalopathy. Example CDH1 variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: CDH1
- Protein: Cadherin-1
- UniProt accession: P12830
- Organism: Homo sapiens
- Variants analyzed: 4399
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 4,304 unspecified-consequence records; 46 synonymous variants; 40 missense variants; 3 frameshift variants; 2 stop-gained variants; 1 splice-region variants; 1 in-frame insertions; 1 in-frame deletions; 1 substitution
- Prediction scores: 1,466 variants have prediction scores (33% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental and epileptic encephalopathy 109, neurodegenerative disease, undetermined early-onset epileptic encephalopathy, hereditary disease, Global developmental delay, lysosomal storage disease, cerebellar ataxia, Hypotonia, Seizure, autism, Miyoshi myopathy, hepatocellular carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 5 domains; 3 binding sites; 21 post-translational modification sites.
- Structural context: 2,726 variants have structural context.
- PTM context: 105 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 CDH1 variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, G2C, G2D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs878854691, ClinGen CA10583399, ClinVar RCV000230267, ClinVar RCV000570172, MetaLR 0.12, MetaSVM -0.95, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- M1K (p.Met1Lys), rs1555509623, ClinGen CA396451188, ClinVar RCV003328484, MetaLR 0.15, MetaSVM -0.80, Pathogenic, CDH1-related diffuse gastric and lobular breast cancer syndrome
- M1L (p.Met1Leu), rs1555509622, ClinGen CA396451179, ClinVar RCV002877435, ClinVar RCV006397147, MetaLR 0.10, MetaSVM -0.95, Likely benign, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- M1R (p.Met1Arg), rs1555509623, ClinGen CA396451182, ClinVar RCV000639275, ClinVar RCV001525446, MetaLR 0.15, MetaSVM -0.80, Pathogenic, CDH1-related diffuse gastric and lobular breast cancer syndrome
- M1T (p.Met1Thr), rs1555509623, ClinGen CA396451185, ClinVar RCV000566678, ClinVar RCV000639234, MetaLR 0.15, MetaSVM -0.80, Pathogenic, CDH1-related diffuse gastric and lobular breast cancer syndrome
- M1V (p.Met1Val), rs1555509622, ClinGen CA396451176, ClinVar RCV000639240, ClinVar RCV002420724, MetaLR 0.10, MetaSVM -0.95, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- G2C (p.Gly2Cys), TOPMed rs786201212, gnomAD rs786201212, Likely benign
- G2D (p.Gly2Asp), rs878854692, ClinGen CA396451206, ClinVar RCV000777434, gnomAD rs878854692, AlphaMissense 0.12, MetaLR 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome
- G2R (p.Gly2Arg), rs786201212, ClinGen CA396451201, ClinVar RCV003625442, TOPMed rs786201212, AlphaMissense 0.23, MetaLR 0.18, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- G2S (p.Gly2Ser), rs786201212, ClinGen CA187442, ClinVar RCV000163100, ClinVar RCV000458853, AlphaMissense 0.23, MetaLR 0.18, Likely benign, CDH1-related diffuse gastric and lobular breast cancer syndrome
- G2V (p.Gly2Val), rs878854692, ClinGen CA10583400, ClinVar RCV000231609, ClinVar RCV002354656, AlphaMissense 0.12, MetaLR 0.13, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- P3A (p.Pro3Ala), Ensembl rs1064793079, Uncertain significance
- P3H (p.Pro3His), ExAC rs587782484, TOPMed rs587782484, gnomAD rs587782484, Likely benign
- P3L (p.Pro3Leu), ExAC rs587782484, TOPMed rs587782484, gnomAD rs587782484, Likely benign
- P3R (p.Pro3Arg), rs587782484, ClinGen CA294410, cosmic curated COSV99028, ClinVar RCV000131602, AlphaMissense 0.08, MetaLR 0.11, Likely benign, CDH1-related diffuse gastric and lobular breast cancer syndrome
- P3S (p.Pro3Ser), rs1064793079, ClinGen CA16620227, ClinVar RCV000485012, ClinVar RCV000817256, AlphaMissense 0.06, MetaLR 0.09, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- P3T (p.Pro3Thr), rs1064793079, ClinGen CA396451215, ClinVar RCV000773783, ClinVar RCV005358006, AlphaMissense 0.06, MetaLR 0.09, Uncertain significance, Ovarian cancer; Familial cancer of breast; Hereditary cancer-predisposing syndro
- W4* (p.Trp4Ter), rs1962423346, ClinGen CA396451240, ClinVar RCV001176687, ClinVar RCV001713069, AlphaMissense 0.04, MetaLR 0.05, Pathogenic
- W4C (p.Trp4Cys), rs1555509636, ClinGen CA396451252, ClinVar RCV003324989, ClinVar RCV004334082, AlphaMissense 0.10, MetaLR 0.06, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- W4G (p.Trp4Gly), rs2543814046, ClinGen CA396451236, ClinVar RCV002303976, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- W4L (p.Trp4Leu), rs1962423346, ClinGen CA396451246, ClinVar RCV002347131, ClinVar RCV006559047, AlphaMissense 0.04, MetaLR 0.05, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- W4S (p.Trp4Ser), Ensembl rs1962423346, MetaLR 0.30, MetaSVM -0.49, Pathogenic
- S5C (p.Ser5Cys), Ensembl rs1555509637, Uncertain significance
- S5G (p.Ser5Gly), rs1555509637, ClinGen CA396451260, ClinVar RCV000559657, ClinVar RCV002395361, AlphaMissense 0.05, MetaLR 0.05, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- S5I (p.Ser5Ile), Ensembl rs998138284, Uncertain significance
- S5N (p.Ser5Asn), rs998138284, ClinGen CA396451266, ClinVar RCV001060669, ClinVar RCV004031926, AlphaMissense 0.08, MetaLR 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- S5R (p.Ser5Arg), rs2543814073, ClinGen CA2580091842, ClinVar RCV003141274, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- R6C (p.Arg6Cys), Ensembl rs2152113958, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- R6G (p.Arg6Gly), Ensembl rs2152113958, Uncertain significance
- R6H (p.Arg6His), rs746464544, NCI-TCGA Cosmic COSV5573, cosmic curated COSV55737, ExAC rs746464544, AlphaMissense 0.12, MetaLR 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- R6L (p.Arg6Leu), rs746464544, ClinGen CA8129772, NCI-TCGA Cosmic COSV5573, ClinVar RCV001344082, AlphaMissense 0.12, MetaLR 0.08, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- R6P (p.Arg6Pro), ExAC rs746464544, gnomAD rs746464544, Uncertain significance
- R6S (p.Arg6Ser), rs2152113958, ClinGen CA396451279, cosmic curated COSV55740, ClinVar RCV002051162, AlphaMissense 0.09, MetaLR 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- R6R (p.Arg6Arg), gnomAD 19-3523008-C-A, CADD 12.70
- R6W (p.Arg6Trp), rs371990144, gnomAD 19-3523008-C-T, REVEL 0.26, MetaLR 0.24
- R6Q (p.Arg6Gln), rs951021097, gnomAD 19-3523009-G-A, REVEL 0.13, MetaLR 0.14
- S7C (p.Ser7Cys), gnomAD rs1303550652, Uncertain significance
- S7G (p.Ser7Gly), rs1303550652, ClinGen CA396451299, ClinVar RCV003229660, gnomAD rs1303550652, AlphaMissense 0.06, MetaLR 0.07, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- S7N (p.Ser7Asn), rs1310934198, ClinGen CA396451305, ClinVar RCV004518892, AlphaMissense 0.08, MetaLR 0.10, Likely benign, Hereditary cancer-predisposing syndrome
- S7R (p.Ser7Arg), rs1555509640, ClinGen CA396451311, ClinVar RCV001525263, Ensembl rs1555509640, AlphaMissense 0.12, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- S7T (p.Ser7Thr), rs1310934198, ClinGen CA396451307, ClinVar RCV001014436, ClinVar RCV001035280, AlphaMissense 0.08, MetaLR 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Familial cancer of breast
- L8F (p.Leu8Phe), rs1234138761, ClinGen CA396451317, ClinVar RCV001916423, ClinVar RCV002449573, AlphaMissense 0.06, MetaLR 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- L8P (p.Leu8Pro), Ensembl rs2152113966
- L8V (p.Leu8Val), rs1234138761, ClinGen CA396451318, ClinVar RCV001015110, ClinVar RCV001369573, AlphaMissense 0.06, MetaLR 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- L8A (p.Leu8Ala), gnomAD 19-3523008-C-CGGC, CADD 33.00
- L8L (p.Leu8Leu), rs2083117661, gnomAD 19-3523014-C-T, CADD 12.90
- S9* (p.Ser9Ter), rs1555509646, ClinGen CA396451339, NCI-TCGA Cosmic COSV5572, cosmic curated COSV55728, AlphaMissense 0.09, MetaLR 0.12, Pathogenic
- S9A (p.Ser9Ala), rs1555509645, ClinGen CA396451336, ClinVar RCV000639268, ClinVar RCV002440262, AlphaMissense 0.07, MetaLR 0.07, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- S9L (p.Ser9Leu), rs1555509646, ClinGen CA396451343, cosmic curated COSV55737, ClinVar RCV000561107, AlphaMissense 0.09, MetaLR 0.12, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- S9P (p.Ser9Pro), TOPMed rs1555509645, not provided, not specified
- S9T (p.Ser9Thr), TOPMed rs1555509645, Uncertain significance
- S9W (p.Ser9Trp), rs1555509646, ClinGen CA396451341, ClinVar RCV003512869, Ensembl rs1555509646, AlphaMissense 0.09, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- A10E (p.Ala10Glu), rs1375360857, ClinGen CA396451352, ClinVar RCV000709391, ClinVar RCV000732057, AlphaMissense 0.42, MetaLR 0.16, Conflicting interpretations, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- A10P (p.Ala10Pro), rs1053572488, ClinGen CA396451350, ClinVar RCV001175961, TOPMed rs1053572488, AlphaMissense 0.12, MetaLR 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- A10T (p.Ala10Thr), rs1053572488, ClinGen CA283273446, ClinVar RCV000804491, ClinVar RCV002440707, AlphaMissense 0.12, MetaLR 0.11, Conflicting interpretations, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- A10V (p.Ala10Val), rs1375360857, ClinGen CA396451354, ClinVar RCV000639226, ClinVar RCV002440261, AlphaMissense 0.42, MetaLR 0.16, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- L11P (p.Leu11Pro), rs1393903966, ClinGen CA396451368, ClinVar RCV001322612, Ensembl rs1393903966, AlphaMissense 0.27, MetaLR 0.21, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- L11Q (p.Leu11Gln), Ensembl rs1393903966, Uncertain significance
- L11R (p.Leu11Arg), rs1393903966, ClinGen CA396451371, ClinVar RCV000709392, ClinVar RCV002458331, AlphaMissense 0.27, MetaLR 0.21, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- L11V (p.Leu11Val), rs2152113973, ClinGen CA396451364, ClinVar RCV002322953, ClinVar RCV006454207, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified
- L11F (p.Leu11Phe), gnomAD 19-3523017-C-T, REVEL 0.07, MetaLR 0.21
- L11L (p.Leu11Leu), gnomAD 19-3523019-T-C, CADD 3.94
- L12P (p.Leu12Pro), rs1191249318, ClinGen CA396451378, ClinVar RCV002008436, gnomAD rs1191249318, AlphaMissense 0.21, MetaLR 0.18, Uncertain significance, Hereditary cancer-predisposing syndrome
- L12Q (p.Leu12Gln), gnomAD rs1191249318, Uncertain significance
- L13V (p.Leu13Val), Ensembl rs2152113977
- L13P (p.Leu13Pro), rs2152113978, ClinGen CA396451393, ClinVar RCV003460367, Ensembl rs2152113978, AlphaMissense 0.23, MetaLR 0.23, Uncertain significance, Familial cancer of breast
- L14M (p.Leu14Met), gnomAD rs1192852993
- L14Q (p.Leu14Gln), Ensembl rs2152113981
- L14V (p.Leu14Val), gnomAD rs1192852993, Conflicting interpretations, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- L15V (p.Leu15Val), gnomAD rs1431383651, Benign
- L15A (p.Leu15Ala), rs2543814251, ClinGen CA2582342541, ClinVar RCV003334670, Pathogenic
- L15P (p.Leu15Pro), ESP rs370614162, TOPMed rs370614162, gnomAD rs370614162, Uncertain significance
- L15Q (p.Leu15Gln), rs370614162, ClinGen CA283273479, ClinVar RCV000699278, ClinVar RCV002257942, AlphaMissense 0.21, MetaLR 0.28, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- Q16* (p.Gln16Ter), rs770244203, ClinGen CA8129776, cosmic curated COSV55739, ClinVar RCV003336875, AlphaMissense 0.09, MetaLR 0.30, Pathogenic
- Q16E (p.Gln16Glu), rs770244203, ClinGen CA396451419, ClinVar RCV002807309, ExAC rs770244203, AlphaMissense 0.09, MetaLR 0.30, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- Q16H (p.Gln16His), rs749591910, ClinGen CA396451427, ClinVar RCV001343962, ClinVar RCV002341708, REVEL 0.07, MetaLR 0.03, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary diffuse gastri
- Q16K (p.Gln16Lys), rs770244203, ClinGen CA396451417, ClinVar RCV002258640, ExAC rs770244203, REVEL 0.13, AlphaMissense 0.09, Conflicting interpretations, Hereditary cancer-predisposing syndrome
- Q16L (p.Gln16Leu), rs775705607, ClinGen CA396451425, ClinVar RCV000772459, ClinVar RCV001219565, AlphaMissense 0.17, MetaLR 0.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- Q16P (p.Gln16Pro), ExAC rs775705607, gnomAD rs775705607, REVEL 0.25, AlphaMissense 0.13, Uncertain significance
- Q16R (p.Gln16Arg), rs775705607, ClinGen CA396451423, ClinVar RCV003040198, ClinVar RCV004603277, AlphaMissense 0.17, MetaLR 0.30, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- Q16Q (p.Gln16Gln), gnomAD 19-3522998-G-A, CADD 11.00
- V17A (p.Val17Ala), Ensembl rs2152114338
- V17D (p.Val17Asp), Ensembl rs2152114338
- V17F (p.Val17Phe), rs780470521, ClinGen CA8129793, cosmic curated COSV55727, ClinVar RCV002343023, AlphaMissense 0.09, MetaLR 0.15, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome
- V17G (p.Val17Gly), Ensembl rs2152114338
- V17L (p.Val17Leu), rs780470521, ClinGen CA16614951, ClinVar RCV000456580, ExAC rs780470521, AlphaMissense 0.09, MetaLR 0.15, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- V17I (p.Val17Ile), rs375035740, gnomAD 19-3523029-G-A, REVEL 0.06, MetaLR 0.01
- V17V (p.Val17Val), gnomAD 19-3523031-C-A, CADD 12.40
- S18P (p.Ser18Pro), Ensembl rs2152114341
- S18Y (p.Ser18Tyr), rs2543816506, ClinGen CA396451600, ClinVar RCV003229711, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- S19A (p.Ser19Ala), rs1042391377, ClinGen CA16614953, ClinVar RCV000465064, ClinVar RCV001024313, AlphaMissense 0.07, MetaLR 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- S19C (p.Ser19Cys), rs1221633501, ClinGen CA396451616, ClinVar RCV000574640, ClinVar RCV001865714, AlphaMissense 0.09, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Endometrial carcinoma; Ovarian cancer
- S19F (p.Ser19Phe), rs1221633501, ClinGen CA396451618, ClinVar RCV001024425, ClinVar RCV001207327, AlphaMissense 0.09, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- S19P (p.Ser19Pro), rs1042391377, NCI-TCGA TCGA novel, ClinGen CA396451608, cosmic curated COSV10437, AlphaMissense 0.07, MetaLR 0.08, Conflicting interpretations, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- S19R (p.Ser19Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S19Y (p.Ser19Tyr), rs1221633501, ClinGen CA396451614, ClinVar RCV001929000, TOPMed rs1221633501, AlphaMissense 0.09, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- W20* (p.Trp20Ter), rs121964875, ClinGen CA280996, cosmic curated COSV55737, ClinVar RCV000013026, AlphaMissense 0.07, MetaLR 0.08, Pathogenic
- W20C (p.Trp20Cys), cosmic curated COSV55737, Ensembl rs786203576, Pathogenic
- W20L (p.Trp20Leu), Ensembl rs121964875, Pathogenic
- W20R (p.Trp20Arg), rs2543816549, ClinGen CA396451624, ClinVar RCV003625881, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- W20S (p.Trp20Ser), rs121964875, ClinGen CA396451633, ClinVar RCV000793152, ClinVar RCV002352316, AlphaMissense 0.07, MetaLR 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- L21F (p.Leu21Phe), rs863224729, ClinGen CA338485, ClinVar RCV000199237, ClinVar RCV001525987, AlphaMissense 0.08, MetaLR 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary diffuse gastri
- L21H (p.Leu21His), Ensembl rs1064794920, Uncertain significance
- L21I (p.Leu21Ile), rs863224729, ClinGen CA10577531, ClinVar RCV000213718, ClinVar RCV000639276, AlphaMissense 0.08, MetaLR 0.11, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- L21P (p.Leu21Pro), rs1064794920, ClinGen CA16620229, ClinVar RCV000486805, ClinVar RCV001525071, AlphaMissense 0.09, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary diffuse gastri
- L21V (p.Leu21Val), rs863224729, ClinGen CA10580066, ClinVar RCV000222019, ClinVar RCV000456561, AlphaMissense 0.08, MetaLR 0.11, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- C22* (p.Cys22Ter), rs865838543, ClinGen CA283274268, ClinVar RCV001951123, gnomAD rs865838543, AlphaMissense 0.34, MetaLR 0.26, Pathogenic
- C22F (p.Cys22Phe), rs1555509758, ClinGen CA396451673, ClinVar RCV003511726, ClinVar RCV005323498, AlphaMissense 0.25, MetaLR 0.21, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- C22R (p.Cys22Arg), Ensembl rs2152114353
- C22S (p.Cys22Ser), Ensembl rs1555509758, Uncertain significance
- C22W (p.Cys22Trp), rs865838543, ClinGen CA396451679, ClinVar RCV001805299, ClinVar RCV003772237, AlphaMissense 0.34, MetaLR 0.26, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- C22Y (p.Cys22Tyr), rs1555509758, ClinGen CA396451671, ClinVar RCV000575835, ClinVar RCV001247235, AlphaMissense 0.25, MetaLR 0.21, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- Q23* (p.Gln23Ter), rs1962456814, ClinGen CA396451685, NCI-TCGA Cosmic COSV5572, cosmic curated COSV55726, AlphaMissense 0.06, MetaLR 0.09, Pathogenic
- Q23E (p.Gln23Glu), NCI-TCGA Cosmic COSV5572, Ensembl rs1962456814, Likely benign, Hereditary cancer-predisposing syndrome
- Q23H (p.Gln23His), TOPMed rs786202657, Benign
- Q23L (p.Gln23Leu), rs1962456890, ClinGen CA396451702, ClinVar RCV001036971, Ensembl rs1962456890, AlphaMissense 0.13, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- Q23P (p.Gln23Pro), Ensembl rs1962456890, Uncertain significance
- Q23R (p.Gln23Arg), Ensembl rs1962456890, Uncertain significance
- E24* (p.Glu24Ter), rs121964876, ClinGen CA280997, cosmic curated COSV55730, ClinVar RCV000013027, AlphaMissense 0.10, MetaLR 0.25, Pathogenic
- E24A (p.Glu24Ala), Ensembl rs2152114362
- E24D (p.Glu24Asp), rs2152114363, Ensembl rs2152114363, ClinGen CA396451740, ClinVar RCV003344138, AlphaMissense 0.12, MetaLR 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome
- E24G (p.Glu24Gly), Ensembl rs2152114362
- E24K (p.Glu24Lys), rs121964876, ClinGen CA396451711, ClinVar RCV001026038, Ensembl rs121964876, AlphaMissense 0.10, MetaLR 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome
- E24Q (p.Glu24Gln), Ensembl rs121964876, Pathogenic
- E24V (p.Glu24Val), Ensembl rs2152114362
- E24E (p.Glu24Glu), rs776991909, gnomAD 19-3523043-G-A, CADD 8.66
- P25A (p.Pro25Ala), Ensembl rs2152114365
- P25L (p.Pro25Leu), rs1485238301, ClinGen CA396451753, ClinVar RCV001026504, ClinVar RCV001230187, AlphaMissense 0.09, MetaLR 0.12, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- P25Q (p.Pro25Gln), gnomAD rs1485238301, Uncertain significance
- P25R (p.Pro25Arg), gnomAD rs1485238301, Uncertain significance
- P25S (p.Pro25Ser), Ensembl rs2152114365
- P25T (p.Pro25Thr), rs1454715253, gnomAD 19-3523053-C-A, REVEL 0.16, MetaLR 0.04
- P25P (p.Pro25Pro), rs1157754673, gnomAD 19-3523055-A-G, CADD 0.46
- E26* (p.Glu26Ter), rs786201058, ClinGen CA186314, cosmic curated COSV55736, ClinVar RCV000162463, AlphaMissense 0.08, MetaLR 0.15, Pathogenic
- E26A (p.Glu26Ala), Ensembl rs2152114371
- E26D (p.Glu26Asp), rs2152114373, Ensembl rs2152114373, ClinGen CA396451778, ClinVar RCV002968085, AlphaMissense 0.12, MetaLR 0.12, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- E26G (p.Glu26Gly), Ensembl rs2152114371
- E26K (p.Glu26Lys), rs786201058, ClinGen CA396451761, cosmic curated COSV55731, ClinVar RCV001026730, AlphaMissense 0.08, MetaLR 0.15, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- E26Q (p.Glu26Gln), rs786201058, ClinGen CA10580068, ClinVar RCV000223374, ClinVar RCV000410130, AlphaMissense 0.08, MetaLR 0.15, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- E26V (p.Glu26Val), Ensembl rs2152114371, MetaLR 0.01, MetaSVM -1.05
- P27A (p.Pro27Ala), Ensembl rs878854696, Likely benign, Hereditary cancer-predisposing syndrome
- P27H (p.Pro27His), TOPMed rs1597838536, Uncertain significance
- P27L (p.Pro27Leu), rs1597838536, ClinGen CA396451791, ClinVar RCV001027177, ClinVar RCV001224958, AlphaMissense 0.09, MetaLR 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- P27S (p.Pro27Ser), rs878854696, ClinGen CA10583401, ClinVar RCV000226798, ClinVar RCV000582299, AlphaMissense 0.09, MetaLR 0.08, Uncertain significance, CDH1-related diffuse gastric and lobular breast cancer syndrome
- P27T (p.Pro27Thr), Ensembl rs878854696, Uncertain significance, Hereditary cancer-predisposing syndrome
- C28* (p.Cys28Ter), rs587780789, ClinGen CA396451818, ClinVar RCV002447702, ClinVar RCV003336576, AlphaMissense 0.87, MetaLR 0.64, Pathogenic
- C28A (p.Cys28Ala), rs2543816722, ClinGen CA645569991, ClinVar RCV003336883, Pathogenic
- C28G (p.Cys28Gly), Ensembl rs2152114380
- C28R (p.Cys28Arg), Ensembl rs2152114380
- C28S (p.Cys28Ser), Ensembl rs2152114382, Uncertain significance
- C28W (p.Cys28Trp), TOPMed rs587780789, gnomAD rs587780789, Pathogenic
- C28Y (p.Cys28Tyr), rs2152114382, ClinGen CA396451809, ClinVar RCV003229736, ClinVar RCV004765780, AlphaMissense 0.88, MetaLR 0.66, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; not provided; Hereditary cancer-predi
- H29D (p.His29Asp), TOPMed rs1254266267, gnomAD rs1254266267, Uncertain significance
- H29L (p.His29Leu), rs1555509761, ClinGen CA396451842, ClinVar RCV001944650, ClinVar RCV004040347, AlphaMissense 0.06, MetaLR 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- H29P (p.His29Pro), Ensembl rs1555509761, Uncertain significance
- H29Q (p.His29Gln), rs1555509762, ClinGen CA396451845, ClinVar RCV001804275, ClinVar RCV001869502, AlphaMissense 0.09, MetaLR 0.03, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- H29R (p.His29Arg), rs1555509761, ClinGen CA396451840, ClinVar RCV000639282, ClinVar RCV000772600, AlphaMissense 0.06, MetaLR 0.02, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- H29Y (p.His29Tyr), rs1254266267, ClinGen CA396451833, ClinVar RCV000698861, TOPMed rs1254266267, AlphaMissense 0.08, MetaLR 0.07, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- P30A (p.Pro30Ala), 1000Genomes rs139866691, ESP rs139866691, ExAC rs139866691, TOPMed rs139866691, Benign
- P30L (p.Pro30Leu), gnomAD rs876660408, Uncertain significance
- P30R (p.Pro30Arg), rs876660408, ClinGen CA10580069, cosmic curated COSV55739, ClinVar RCV000214994, AlphaMissense 0.19, MetaLR 0.73, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- P30S (p.Pro30Ser), rs139866691, ClinGen CA396451854, cosmic curated COSV55739, ClinVar RCV001891102, AlphaMissense 0.15, MetaLR 0.55, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- P30T (p.Pro30Thr), rs139866691, ClinGen CA151524, cosmic curated COSV10455, ClinVar RCV000115864, AlphaMissense 0.15, MetaLR 0.55, Benign, CDH1-related diffuse gastric and lobular breast cancer syndrome
- P30P (p.Pro30Pro), rs138345484, gnomAD 19-3525897-T-C, CADD 2.00
- G31A (p.Gly31Ala), rs1131690823, ClinGen CA396451875, ClinVar RCV000816009, Ensembl rs1131690823, AlphaMissense 0.71, MetaLR 0.42, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- G31C (p.Gly31Cys), Ensembl rs2152114387, Uncertain significance
- G31D (p.Gly31Asp), rs1131690823, ClinGen CA396451873, ClinVar RCV001019135, ClinVar RCV001223352, AlphaMissense 0.71, MetaLR 0.42, Uncertain significance, Familial cancer of breast; Hereditary cancer-predisposing syndrome; Hereditary d
- G31R (p.Gly31Arg), Ensembl rs2152114387, Uncertain significance
- G31S (p.Gly31Ser), rs2152114387, ClinGen CA396451864, ClinVar RCV001368687, Ensembl rs2152114387, AlphaMissense 0.29, MetaLR 0.39, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- G31V (p.Gly31Val), rs1131690823, ClinGen CA396451877, ClinVar RCV000492686, ClinVar RCV000639264, AlphaMissense 0.71, MetaLR 0.42, Likely benign, CDH1-related diffuse gastric and lobular breast cancer syndrome
- F32I (p.Phe32Ile), rs1382043754, ClinVar RCV004575509, ClinVar RCV005101923, TOPMed rs1382043754, AlphaMissense 0.88, MetaLR 0.59, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Familial cancer of breast
- F32L (p.Phe32Leu), TOPMed rs1382043754, gnomAD rs1382043754, Uncertain significance, Hereditary cancer-predisposing syndrome
- F32S (p.Phe32Ser), Ensembl rs2152114393
- D33A (p.Asp33Ala), Ensembl rs1597838602, Likely benign
- D33E (p.Asp33Glu), rs1597838607, Ensembl rs1597838607, ClinGen CA396451935, ClinVar RCV001019968, AlphaMissense 0.13, MetaLR 0.03, Uncertain significance, Hereditary cancer-predisposing syndrome
- D33G (p.Asp33Gly), Ensembl rs1597838602, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary diffuse gastric adenocarcino
- D33H (p.Asp33His), Ensembl rs2152114394
- D33N (p.Asp33Asn), Ensembl rs2152114394, Uncertain significance, Hereditary diffuse gastric adenocarcinoma; Hereditary cancer-predisposing syndro
- D33V (p.Asp33Val), rs1597838602, ClinGen CA396451930, ClinVar RCV000812190, Ensembl rs1597838602, AlphaMissense 0.14, MetaLR 0.06, Uncertain significance, Hereditary diffuse gastric adenocarcinoma
- D33Y (p.Asp33Tyr), Ensembl rs2152114394, MetaLR 0.03, MetaSVM -1.06, Uncertain significance, Hereditary cancer-predisposing syndrome
Public CDH1 analysis runs
- CDH1 analysis run — CDH1 (4,399 variants) — completed 2026-08-18