FAT1 (Protocadherin Fat 1) variants and mutations
FAT1 (also known as Protocadherin Fat 1) is a human protein-coding gene encoding a protocadherin Fat 1 protein. Its annotated function is plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. It is annotated at the cell membrane. This analysis covers 19,483 FAT1 variants and mutations. Of these, 30% have computational variant effect predictions. Disease context includes head and neck squamous cell carcinoma, squamous cell lung carcinoma, and cervical squamous cell carcinoma. Example FAT1 variants include G2A, G2E, and G2R.
Variant analysis overview
- Gene: FAT1
- Protein: Protocadherin Fat 1
- UniProt accession: Q14517
- Organism: Homo sapiens
- Variants analyzed: 19483
- Variant scope: all variants
- Completed: 2026-09-10
Variant and mutation evidence
- Variant composition: 19,511 unspecified-consequence records; 112 synonymous variants; 8 frameshift variants; 33 missense variants; 6 in-frame deletions; 1 in-frame insertions; 1 substitution
- Prediction scores: 5,829 variants have prediction scores (30% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: head and neck squamous cell carcinoma, squamous cell lung carcinoma, cervical squamous cell carcinoma, hereditary disease, nasopharyngeal neoplasm, urinary bladder cancer, cutaneous squamous cell carcinoma, focal segmental glomerulosclerosis, nephrotic syndrome, non-small cell lung carcinoma, esophageal squamous cell carcinoma, esophageal cancer.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 39 domains; 22 post-translational modification sites.
- Structural context: 16,094 variants have structural context.
- PTM context: 94 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable FAT1 variants
Examples include G2A, G2E, G2R, G2V, G2W, R3I, R3K, R3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2A (p.Gly2Ala), Ensembl rs1561012710
- G2E (p.Gly2Glu), cosmic curated COSV71672, Ensembl rs1561012710, REVEL 0.16, CADD 16.30
- G2R (p.Gly2Arg), Ensembl rs2126706998
- G2V (p.Gly2Val), cosmic curated COSV71676, Ensembl rs1561012710, REVEL 0.29, CADD 23.00
- G2W (p.Gly2Trp), Ensembl rs2126706998, REVEL 0.30, CADD 24.30
- R3I (p.Arg3Ile), Ensembl rs1579493255, REVEL 0.15, CADD 20.30
- R3K (p.Arg3Lys), Ensembl rs1579493255
- R3S (p.Arg3Ser), 1000Genomes rs371512264, ESP rs371512264, ExAC rs371512264, TOPMed rs371512264, Likely benign
- R3T (p.Arg3Thr), Ensembl rs1579493255
- H4D (p.His4Asp), ExAC rs760534470, gnomAD rs760534470
- H4L (p.His4Leu), Ensembl rs2126706946
- H4N (p.His4Asn), ExAC rs760534470, gnomAD rs760534470, REVEL 0.09, CADD 12.80
- H4P (p.His4Pro), Ensembl rs2126706946
- H4Y (p.His4Tyr), ExAC rs760534470, gnomAD rs760534470, REVEL 0.16, CADD 7.66
- L5F (p.Leu5Phe), Ensembl rs1744867387, REVEL 0.08, CADD 13.20
- A6G (p.Ala6Gly), Ensembl rs2126706899, CADD 6.39
- A6P (p.Ala6Pro), Ensembl rs2126706908
- A6S (p.Ala6Ser), Ensembl rs2126706908, REVEL 0.05, CADD 6.48
- A6T (p.Ala6Thr), Ensembl rs2126706908, REVEL 0.07, CADD 7.79
- A6V (p.Ala6Val), Ensembl rs2126706899, REVEL 0.05, CADD 15.10
- L7* (p.Leu7Ter), Ensembl rs2126706883
- L7F (p.Leu7Phe), Ensembl rs2126706875, REVEL 0.18, CADD 5.31
- L8F (p.Leu8Phe), cosmic curated COSV71676, Ensembl rs1744867198, REVEL 0.24, CADD 13.30
- L8H (p.Leu8His), ExAC rs767545930, gnomAD rs767545930
- L8P (p.Leu8Pro), ExAC rs767545930, gnomAD rs767545930, REVEL 0.38, CADD 17.50
- L9P (p.Leu9Pro), Ensembl rs2126706840
- L9Q (p.Leu9Gln), Ensembl rs2126706840
- L9V (p.Leu9Val), Ensembl rs2126706851
- L10F (p.Leu10Phe), gnomAD rs1401666091, REVEL 0.25, CADD 22.70
- L10H (p.Leu10His), 1000Genomes rs202138193, ExAC rs202138193, TOPMed rs202138193, gnomAD rs202138193
- L10P (p.Leu10Pro), 1000Genomes rs202138193, ExAC rs202138193, TOPMed rs202138193, gnomAD rs202138193, REVEL 0.42, CADD 22.60
- L10R (p.Leu10Arg), 1000Genomes rs202138193, ExAC rs202138193, TOPMed rs202138193, gnomAD rs202138193
- L10V (p.Leu10Val), gnomAD rs1401666091
- L11P (p.Leu11Pro), Ensembl rs2126706784, REVEL 0.47, CADD 24.60
- L11Q (p.Leu11Gln), Ensembl rs2126706784
- L11V (p.Leu11Val), Ensembl rs2126706796
- L12F (p.Leu12Phe), Ensembl rs2126706761, REVEL 0.25, CADD 17.40
- L12P (p.Leu12Pro), Ensembl rs2126706756
- L12V (p.Leu12Val), Ensembl rs2126706761
- L13F (p.Leu13Phe), Ensembl rs2126706741
- L13H (p.Leu13His), ExAC rs770523514, gnomAD rs770523514
- L13I (p.Leu13Ile), Ensembl rs2126706741
- L13P (p.Leu13Pro), ExAC rs770523514, gnomAD rs770523514
- L13R (p.Leu13Arg), ExAC rs770523514, gnomAD rs770523514, REVEL 0.37, CADD 17.80
- L13V (p.Leu13Val), Ensembl rs2126706741
- L14F (p.Leu14Phe), TOPMed rs1458285250, gnomAD rs1458285250, REVEL 0.16, CADD 16.60
- L14H (p.Leu14His), Ensembl rs2126706704
- L14P (p.Leu14Pro), Ensembl rs2126706704
- F15L (p.Phe15Leu), TOPMed rs985061273, gnomAD rs985061273, REVEL 0.17, CADD 7.67
- Q16* (p.Gln16Ter), cosmic curated COSV71671, Ensembl rs2126706680
- Q16E (p.Gln16Glu), Ensembl rs2126706680
- Q16H (p.Gln16His), Ensembl rs1744865204
- Q16K (p.Gln16Lys), Ensembl rs2126706680
- Q16L (p.Gln16Leu), Ensembl rs2126706674
- H17D (p.His17Asp), ExAC rs750299667, TOPMed rs750299667, gnomAD rs750299667, REVEL 0.24, CADD 15.10
- H17L (p.His17Leu), ExAC rs770129683, gnomAD rs770129683
- H17R (p.His17Arg), ExAC rs770129683, gnomAD rs770129683, REVEL 0.09, CADD 0.93
- H17Y (p.His17Tyr), ExAC rs750299667, TOPMed rs750299667, gnomAD rs750299667, REVEL 0.18, CADD 13.50
- F18L (p.Phe18Leu), Ensembl rs2126706623
- F18S (p.Phe18Ser), Ensembl rs2126706636
- F18Y (p.Phe18Tyr), Ensembl rs2126706636
- G19A (p.Gly19Ala), rs200192750, ClinGen CA3167738, ClinVar RCV002124337, ClinVar RCV004553807, REVEL 0.14, CADD 5.31, Conflicting interpretations, Inborn genetic diseases; FAT1-related disorder; not provided
- G19E (p.Gly19Glu), 1000Genomes rs200192750, ESP rs200192750, ExAC rs200192750, TOPMed rs200192750, REVEL 0.22, CADD 6.42, Likely benign
- G19V (p.Gly19Val), 1000Genomes rs200192750, ESP rs200192750, ExAC rs200192750, TOPMed rs200192750, REVEL 0.20, CADD 8.73, Likely benign
- D20E (p.Asp20Glu), ExAC rs781709536, gnomAD rs781709536
- D20G (p.Asp20Gly), Ensembl rs2126706598
- D20H (p.Asp20His), Ensembl rs2126706605
- D20N (p.Asp20Asn), Ensembl rs2126706605, REVEL 0.07, CADD 10.80
- D20V (p.Asp20Val), Ensembl rs2126706598
- D20Y (p.Asp20Tyr), Ensembl rs2126706605
- S21C (p.Ser21Cys), Ensembl rs2126706585, REVEL 0.16, CADD 0.76
- S21G (p.Ser21Gly), Ensembl rs2126706585
- S21I (p.Ser21Ile), Ensembl rs1744863893
- S21N (p.Ser21Asn), Ensembl rs1744863893
- S21R (p.Ser21Arg), Ensembl rs2126706573
- S21T (p.Ser21Thr), Ensembl rs1744863893, REVEL 0.13, CADD 11.80
- D22E (p.Asp22Glu), Ensembl rs2126706552
- D22G (p.Asp22Gly), Ensembl rs2126706563
- D22H (p.Asp22His), Ensembl rs919270098
- D22N (p.Asp22Asn), Ensembl rs919270098
- D22V (p.Asp22Val), Ensembl rs2126706563
- D22Y (p.Asp22Tyr), Ensembl rs919270098
- G23A (p.Gly23Ala), ExAC rs769132614, gnomAD rs769132614
- G23C (p.Gly23Cys), Ensembl rs2126706542
- G23D (p.Gly23Asp), rs769132614, ExAC rs769132614, gnomAD rs769132614, REVEL 0.19, CADD 22.80, Variant assessed as somatic; moderate impact.
- G23R (p.Gly23Arg), Ensembl rs2126706542
- G23S (p.Gly23Ser), Ensembl rs2126706542
- G23V (p.Gly23Val), ExAC rs769132614, gnomAD rs769132614
- S24C (p.Ser24Cys), Ensembl rs2126706526
- S24I (p.Ser24Ile), Ensembl rs2126706517
- S24N (p.Ser24Asn), cosmic curated COSV71674, Ensembl rs2126706517
- S24R (p.Ser24Arg), ExAC rs747121240, gnomAD rs747121240, REVEL 0.14, CADD 16.50
- S24T (p.Ser24Thr), Ensembl rs2126706517
- Q25* (p.Gln25Ter), Ensembl rs2126706503
- Q25E (p.Gln25Glu), Ensembl rs2126706503
- Q25H (p.Gln25His), TOPMed rs942010820, gnomAD rs942010820
- Q25K (p.Gln25Lys), Ensembl rs2126706503
- Q25R (p.Gln25Arg), ExAC rs780057288, gnomAD rs780057288, REVEL 0.06, CADD 10.80
- R26* (p.Arg26Ter), cosmic curated COSV10606, TOPMed rs1579493035, CADD 31.00
- R26G (p.Arg26Gly), TOPMed rs1579493035
- R26L (p.Arg26Leu), 1000Genomes rs75367100, ESP rs75367100, ExAC rs75367100, TOPMed rs75367100, REVEL 0.05, CADD 10.50, Benign
- R26P (p.Arg26Pro), 1000Genomes rs75367100, ESP rs75367100, ExAC rs75367100, TOPMed rs75367100, Benign
- R26Q (p.Arg26Gln), rs75367100, ClinGen CA3167733, cosmic curated COSV71675, ClinVar RCV001684675, REVEL 0.07, CADD 9.36, Benign, not provided; not specified
- L27H (p.Leu27His), ExAC rs750588830, gnomAD rs750588830
- L27P (p.Leu27Pro), cosmic curated COSV11654, ExAC rs750588830, gnomAD rs750588830
- L27V (p.Leu27Val), Ensembl rs2126706459
- E28* (p.Glu28Ter), NCI-TCGA Cosmic COSV1014, cosmic curated COSV10149, Ensembl rs2126706432, Variant assessed as somatic; high impact.
- E28A (p.Glu28Ala), Ensembl rs2126706426
- E28D (p.Glu28Asp), cosmic curated COSV11654, Ensembl rs2126706422
- E28K (p.Glu28Lys), Ensembl rs2126706432, REVEL 0.14, CADD 15.10
- E28Q (p.Glu28Gln), Ensembl rs2126706432
- E28V (p.Glu28Val), Ensembl rs2126706426
- Q29* (p.Gln29Ter), NCI-TCGA Cosmic COSV1014, cosmic curated COSV10149, ESP rs372397939, ExAC rs372397939, Variant assessed as somatic; high impact.
- Q29E (p.Gln29Glu), ESP rs372397939, ExAC rs372397939, TOPMed rs372397939, gnomAD rs372397939, REVEL 0.17, CADD 6.75, Uncertain significance, Inborn genetic diseases
- Q29H (p.Gln29His), Ensembl rs2126706381
- Q29K (p.Gln29Lys), ESP rs372397939, ExAC rs372397939, TOPMed rs372397939, gnomAD rs372397939
- Q29L (p.Gln29Leu), gnomAD rs1260299833
- Q29R (p.Gln29Arg), gnomAD rs1260299833
- T30A (p.Thr30Ala), Ensembl rs2126706378
- T30I (p.Thr30Ile), Ensembl rs1744861328
- T30P (p.Thr30Pro), Ensembl rs2126706378
- T30S (p.Thr30Ser), Ensembl rs2126706378
- P31A (p.Pro31Ala), gnomAD rs1217025404, REVEL 0.10, CADD 14.70
- P31S (p.Pro31Ser), gnomAD rs1217025404, REVEL 0.10, CADD 15.70
- L32Q (p.Leu32Gln), Ensembl rs2126706337
- L32V (p.Leu32Val), TOPMed rs1231978552, gnomAD rs1231978552, REVEL 0.14, CADD 0.03
- Q33* (p.Gln33Ter), cosmic curated COSV71674, Ensembl rs1744860338
- Q33E (p.Gln33Glu), Ensembl rs1744860338
- Q33H (p.Gln33His), Ensembl rs2126706311
- Q33K (p.Gln33Lys), Ensembl rs1744860338
- Q33L (p.Gln33Leu), gnomAD rs1744860131
- Q33R (p.Gln33Arg), gnomAD rs1744860131, REVEL 0.16, CADD 17.40
- F34C (p.Phe34Cys), Ensembl rs2126706295
- F34I (p.Phe34Ile), TOPMed rs1294508999, gnomAD rs1294508999
- F34L (p.Phe34Leu), TOPMed rs1294508999, gnomAD rs1294508999, REVEL 0.71, CADD 26.20
- F34Y (p.Phe34Tyr), Ensembl rs2126706295
- T35I (p.Thr35Ile), ExAC rs752517403, gnomAD rs752517403, REVEL 0.52, CADD 25.20
- T35K (p.Thr35Lys), ExAC rs752517403, gnomAD rs752517403
- T35R (p.Thr35Arg), ExAC rs752517403, gnomAD rs752517403
- H36D (p.His36Asp), ExAC rs767601213, gnomAD rs767601213
- H36L (p.His36Leu), TOPMed rs1460512791, gnomAD rs1460512791, CADD 0.07
- H36P (p.His36Pro), TOPMed rs1460512791, gnomAD rs1460512791
- H36Q (p.His36Gln), ESP rs368755360, ExAC rs368755360, TOPMed rs368755360, gnomAD rs368755360
- H36R (p.His36Arg), TOPMed rs1460512791, gnomAD rs1460512791, CADD 0.07
- H36Y (p.His36Tyr), ExAC rs767601213, gnomAD rs767601213, REVEL 0.23, CADD 20.00
- L37H (p.Leu37His), Ensembl rs2126706237
- L37I (p.Leu37Ile), TOPMed rs1164804404
- L37P (p.Leu37Pro), Ensembl rs2126706237, REVEL 0.14, CADD 8.38
- E38* (p.Glu38Ter), NCI-TCGA Cosmic COSV1014, cosmic curated COSV10149, ExAC rs751034262, Uncertain significance
- E38D (p.Glu38Asp), TOPMed rs1744857974
- E38K (p.Glu38Lys), rs751034262, ClinGen CA3167725, NCI-TCGA Cosmic COSV1014, REVEL 0.24, CADD 15.70, Uncertain significance, Inborn genetic diseases; not provided
- E38Q (p.Glu38Gln), ExAC rs751034262, TOPMed rs751034262, gnomAD rs751034262, Uncertain significance
- E38V (p.Glu38Val), Ensembl rs2126706224
- Y39* (p.Tyr39Ter), Ensembl rs2126706187, cosmic curated COSV11654
- Y39D (p.Tyr39Asp), Ensembl rs2126706206
- Y39F (p.Tyr39Phe), Ensembl rs2126706196
- Y39H (p.Tyr39His), Ensembl rs2126706206
- Y39N (p.Tyr39Asn), cosmic curated COSV10149, Ensembl rs2126706206
- Y39S (p.Tyr39Ser), Ensembl rs2126706196
- N40D (p.Asn40Asp), TOPMed rs1331699793, gnomAD rs1331699793, REVEL 0.20, CADD 18.50
- N40I (p.Asn40Ile), TOPMed rs1401817751
- N40K (p.Asn40Lys), ExAC rs762517018, TOPMed rs762517018, gnomAD rs762517018
- N40S (p.Asn40Ser), cosmic curated COSV10895, TOPMed rs1401817751, REVEL 0.38, CADD 23.50
- N40T (p.Asn40Thr), TOPMed rs1401817751
- N40Y (p.Asn40Tyr), TOPMed rs1331699793, gnomAD rs1331699793
- V41A (p.Val41Ala), Ensembl rs2126706155, CADD 19.20
- V41D (p.Val41Asp), Ensembl rs2126706155
- V41G (p.Val41Gly), Ensembl rs2126706155
- V41I (p.Val41Ile), rs371144856, cosmic curated COSV10753, ESP rs371144856, ExAC rs371144856, REVEL 0.18, CADD 20.10, Variant assessed as somatic; moderate impact.
- T42A (p.Thr42Ala), ExAC rs764788007, gnomAD rs764788007, REVEL 0.41, CADD 24.00
- T42I (p.Thr42Ile), cosmic curated COSV71672, ESP rs377614281, ExAC rs377614281, TOPMed rs377614281, Uncertain significance
- T42N (p.Thr42Asn), ESP rs377614281, ExAC rs377614281, TOPMed rs377614281, gnomAD rs377614281, CADD 17.20, Uncertain significance, Inborn genetic diseases
- T42S (p.Thr42Ser), ESP rs377614281, ExAC rs377614281, TOPMed rs377614281, gnomAD rs377614281, Uncertain significance
- V43A (p.Val43Ala), TOPMed rs1317768990, gnomAD rs1317768990, REVEL 0.54, CADD 23.00
- V43E (p.Val43Glu), TOPMed rs1317768990, gnomAD rs1317768990
- V43G (p.Val43Gly), TOPMed rs1317768990, gnomAD rs1317768990
- V43L (p.Val43Leu), 1000Genomes rs560660262, ExAC rs560660262, TOPMed rs560660262, gnomAD rs560660262, Uncertain significance
- V43M (p.Val43Met), rs560660262, ClinGen CA3167718, ClinVar RCV003097482, 1000Genomes rs560660262, REVEL 0.37, CADD 23.30, Uncertain significance, not provided
- Q44* (p.Gln44Ter), cosmic curated COSV11654, Ensembl rs2126706091
- Q44E (p.Gln44Glu), Ensembl rs2126706091
Public FAT1 analysis runs
- FAT1 analysis run — FAT1 (19,483 variants) — completed 2026-09-10