YAP1 (Transcriptional coactivator YAP1) variants and mutations
YAP1 (also known as Transcriptional coactivator YAP1) is a human protein-coding gene encoding a transcriptional coactivator protein. When Hippo signaling permits nuclear accumulation, it integrates mechanical, polarity, and growth cues to control proliferation, survival, and organ size. Persistent nuclear YAP activity contributes to many cancers, while germline loss-of-function variants can cause developmental eye abnormalities. This analysis covers 1,002 YAP1 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes uveal coloboma-cleft lip and palate-intellectual disability, Uveal coloboma - cleft lip and palate - intellectual disability, and coloboma. Example YAP1 variants include M1L, D2N, and D2Y.
Variant analysis overview
- Gene: YAP1
- Protein: Transcriptional coactivator YAP1
- UniProt accession: P46937
- Organism: Homo sapiens
- Variants analyzed: 1002
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 639 unspecified-consequence records; 187 missense variants; 131 synonymous variants; 15 frameshift variants; 12 stop-gained variants; 3 in-frame insertions; 9 in-frame deletions; 6 substitution
- Prediction scores: 835 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: uveal coloboma-cleft lip and palate-intellectual disability, Uveal coloboma - cleft lip and palate - intellectual disability, coloboma, neurodegenerative disease, polycystic ovary syndrome, Merkel cell skin cancer, plasma cell myeloma, esophageal adenocarcinoma, hemangioblastoma, lymphoid neoplasm, kidney neoplasm, bile duct carcinoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 25 post-translational modification sites.
- Structural context: 90 variants have structural context.
- PTM context: 50 variants overlap post-translational modification sites.
- Experimental data: 50 protein positions have experimental scores. Source: YAP1 WW domain domainome 1.0.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable YAP1 variants
Examples include M1L, D2N, D2Y, D2G, D2E, D2D, P3L, P3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2135083651, ClinGen CA382490408, ClinVar RCV003238559, Uncertain significance, not provided
- D2N (p.Asp2Asn), Ensembl rs1942848037, REVEL 0.04, CADD 22.80
- D2Y (p.Asp2Tyr), NCI-TCGA TCGA novel, REVEL 0.03, CADD 22.90, Variant assessed as somatic; moderate impact.
- D2G (p.Asp2Gly), gnomAD 11-102110853-A-G, REVEL 0.09, CADD 22.90
- D2E (p.Asp2Glu), gnomAD 11-102110854-T-A, REVEL 0.04, CADD 21.00
- D2D (p.Asp2Asp), gnomAD 11-102110854-T-C, CADD 12.80
- P3L (p.Pro3Leu), Ensembl rs1942848376, REVEL 0.05, CADD 22.50
- P3S (p.Pro3Ser), TOPMed rs1319669560, gnomAD rs1319669560, REVEL 0.05, CADD 19.90
- P3T (p.Pro3Thr), TOPMed rs1319669560, gnomAD rs1319669560, REVEL 0.03, CADD 19.40
- P3H (p.Pro3His), gnomAD 11-102110856-C-A, REVEL 0.08, CADD 22.50
- P3P (p.Pro3Pro), rs1448858275, gnomAD 11-102110857-C-A, CADD 9.21
- G4A (p.Gly4Ala), TOPMed rs867829919, gnomAD rs867829919, REVEL 0.08, CADD 19.30, Uncertain significance, not specified
- G4E (p.Gly4Glu), rs867829919, ClinGen CA228282917, ClinVar RCV003398133, TOPMed rs867829919, REVEL 0.07, CADD 20.40, Uncertain significance, not provided
- G4R (p.Gly4Arg), TOPMed rs972415996, REVEL 0.06, CADD 22.40
- G4W (p.Gly4Trp), gnomAD 11-102110858-G-T, REVEL 0.05, CADD 22.80
- G4V (p.Gly4Val), gnomAD 11-102110859-G-T, REVEL 0.08, CADD 20.10
- G4G (p.Gly4Gly), gnomAD 11-102110860-G-A, CADD 13.20
- Q5L (p.Gln5Leu), gnomAD rs1279185601, REVEL 0.09, CADD 24.80
- Q5S (p.Gln5Ser), gnomAD 11-102110854-TC-T, CADD 22.90
- Q5K (p.Gln5Lys), gnomAD 11-102110861-C-A, REVEL 0.06, CADD 23.60
- Q5* (p.Gln5Ter), gnomAD 11-102110861-C-T, CADD 36.00
- Q5R (p.Gln5Arg), gnomAD 11-102110862-A-G, REVEL 0.07, CADD 24.30
- Q5H (p.Gln5His), gnomAD 11-102110863-G-T, REVEL 0.13, CADD 24.10
- Q5Q (p.Gln5Gln), gnomAD 11-102110863-G-A, CADD 11.60
- Q6* (p.Gln6Ter), gnomAD 11-102110864-C-T, CADD 36.00
- Q6K (p.Gln6Lys), gnomAD 11-102110864-C-A, REVEL 0.05, CADD 22.60
- Q6E (p.Gln6Glu), gnomAD 11-102110864-C-G, REVEL 0.07, CADD 22.20
- Q6R (p.Gln6Arg), gnomAD 11-102110865-A-G, REVEL 0.06, CADD 22.50
- Q6H (p.Gln6His), gnomAD 11-102110866-G-T, REVEL 0.04, CADD 21.50
- Q6Q (p.Gln6Gln), gnomAD 11-102110866-G-A, CADD 11.20
- P7L (p.Pro7Leu), rs1025759993, ClinGen CA228282918, ClinVar RCV003112879, TOPMed rs1025759993, REVEL 0.03, CADD 21.40, Uncertain significance, not provided
- P7S (p.Pro7Ser), Ensembl rs1255639415, REVEL 0.06, CADD 22.20
- P7T (p.Pro7Thr), Ensembl rs1255639415, REVEL 0.04, CADD 21.70
- P7Q (p.Pro7Gln), gnomAD 11-102110868-C-A, REVEL 0.07, CADD 22.90
- P7P (p.Pro7Pro), rs775598673, gnomAD 11-102110869-G-A, CADD 13.50
- P8S (p.Pro8Ser), gnomAD rs1230599890, REVEL 0.08, CADD 23.30
- P8R (p.Pro8Arg), gnomAD 11-102110869-GC-G, CADD 23.00
- P8T (p.Pro8Thr), gnomAD 11-102110870-C-A, REVEL 0.07, CADD 23.10
- P8Q (p.Pro8Gln), gnomAD 11-102110871-C-A, REVEL 0.08, CADD 23.50
- P8L (p.Pro8Leu), gnomAD 11-102110871-C-T, REVEL 0.07, CADD 23.80
- P8P (p.Pro8Pro), gnomAD 11-102110872-G-T, CADD 12.50
- P9L (p.Pro9Leu), TOPMed rs1942849865, gnomAD rs1942849865, REVEL 0.05, CADD 22.70
- P9S (p.Pro9Ser), Ensembl rs1250761343, REVEL 0.04, CADD 22.40
- p.Pro9dup, gnomAD 11-102110865-A-AG, CADD 17.20
- p.Pro9 Pro24del, gnomAD 11-102110869-GCCG, CADD 18.10
- P9T (p.Pro9Thr), gnomAD 11-102110873-C-A, REVEL 0.04, CADD 22.10
- P9H (p.Pro9His), gnomAD 11-102110874-C-A, REVEL 0.07, CADD 22.60
- P9P (p.Pro9Pro), gnomAD 11-102110875-T-C, CADD 14.20
- Q10K (p.Gln10Lys), gnomAD rs1323319846, REVEL 0.06, CADD 21.40
- Q10* (p.Gln10Ter), gnomAD 11-102110876-C-T, CADD 35.00
- Q10R (p.Gln10Arg), gnomAD 11-102110877-A-G, REVEL 0.04, CADD 22.20
- Q10L (p.Gln10Leu), gnomAD 11-102110877-A-T, REVEL 0.02, CADD 22.60
- Q10P (p.Gln10Pro), gnomAD 11-102110877-A-C, REVEL 0.04, CADD 22.40
- Q10H (p.Gln10His), gnomAD 11-102110878-A-C, REVEL 0.02, CADD 19.20
- Q10Q (p.Gln10Gln), rs981664113, gnomAD 11-102110878-A-G, CADD 10.80
- P11A (p.Pro11Ala), gnomAD rs1281367129, REVEL 0.01, CADD 16.10
- P11L (p.Pro11Leu), 1000Genomes rs2135084131, REVEL 0.03, CADD 22.50
- P11S (p.Pro11Ser), gnomAD rs1281367129, REVEL 0.01, CADD 17.50
- P11T (p.Pro11Thr), gnomAD 11-102110879-C-A, REVEL 0.01, CADD 17.00
- P11Q (p.Pro11Gln), gnomAD 11-102110880-C-A, REVEL 0.03, CADD 22.30
- P11P (p.Pro11Pro), rs747081306, gnomAD 11-102110881-G-A, CADD 13.40
- A12P (p.Ala12Pro), rs927540361, Ensembl rs927540361, REVEL 0.06, CADD 22.70, Variant assessed as somatic; moderate impact.
- A12V (p.Ala12Val), TOPMed rs1180551289, gnomAD rs1180551289, REVEL 0.05, CADD 19.70
- p.Ala12 Pro13del, gnomAD 11-102110878-ACCG, CADD 16.60
- A12T (p.Ala12Thr), gnomAD 11-102110882-G-A, REVEL 0.06, CADD 22.60
- A12S (p.Ala12Ser), gnomAD 11-102110882-G-T, REVEL 0.07, CADD 22.00
- A12D (p.Ala12Asp), gnomAD 11-102110883-C-A, REVEL 0.05, CADD 19.70
- A12G (p.Ala12Gly), gnomAD 11-102110883-C-G, REVEL 0.04, CADD 19.60
- A12A (p.Ala12Ala), gnomAD 11-102110884-C-A, CADD 12.10
- P13R (p.Pro13Arg), TOPMed rs1255203435, gnomAD rs1255203435, REVEL 0.04, CADD 22.60
- P13T (p.Pro13Thr), cosmic curated COSV99176, REVEL 0.03, CADD 19.70
- P13S (p.Pro13Ser), gnomAD 11-102110885-C-T, REVEL 0.07, CADD 16.40
- P13H (p.Pro13His), gnomAD 11-102110886-C-A, REVEL 0.05, CADD 22.60
- P13L (p.Pro13Leu), gnomAD 11-102110886-C-T, REVEL 0.04, CADD 22.80
- P13P (p.Pro13Pro), rs776906339, gnomAD 11-102110887-C-A, CADD 13.50
- Q14K (p.Gln14Lys), TOPMed rs1182593083, gnomAD rs1182593083, REVEL 0.08, CADD 22.20
- Q14G (p.Gln14Gly), gnomAD 11-102110882-GCC-, CADD 22.60
- Q14P (p.Gln14Pro), gnomAD 11-102110882-G-GC, CADD 23.90
- Q14R (p.Gln14Arg), rs1555075248, gnomAD 11-102110882-GC-G, CADD 22.40
- Q14E (p.Gln14Glu), gnomAD 11-102110888-C-G, REVEL 0.09, CADD 21.50
- Q14* (p.Gln14Ter), gnomAD 11-102110888-C-T, CADD 35.00
- Q14L (p.Gln14Leu), gnomAD 11-102110889-A-T, REVEL 0.04, CADD 21.90
- Q14H (p.Gln14His), gnomAD 11-102110890-G-T, REVEL 0.06, CADD 23.00
- Q14Q (p.Gln14Gln), rs1942851760, gnomAD 11-102110890-G-A, CADD 12.50
- G15D (p.Gly15Asp), ExAC rs762152510, TOPMed rs762152510, gnomAD rs762152510, REVEL 0.05, CADD 22.90
- G15S (p.Gly15Ser), TOPMed rs1428291984, gnomAD rs1428291984, REVEL 0.06, CADD 20.00
- G15A (p.Gly15Ala), gnomAD 11-102110889-AG-A, CADD 24.90
- G15C (p.Gly15Cys), gnomAD 11-102110891-G-T, REVEL 0.09, CADD 21.80
- G15V (p.Gly15Val), gnomAD 11-102110892-G-T, REVEL 0.04, CADD 22.90
- G15G (p.Gly15Gly), gnomAD 11-102110893-C-T, CADD 13.90
- Q16H (p.Gln16His), TOPMed rs1353903423, REVEL 0.01, CADD 20.20, Uncertain significance, not specified
- Q16K (p.Gln16Lys), gnomAD 11-102110892-GC-G, CADD 23.30
- Q16* (p.Gln16Ter), gnomAD 11-102110894-C-T, CADD 35.00
- Q16R (p.Gln16Arg), gnomAD 11-102110895-A-G, REVEL 0.04, CADD 17.90
- Q16Q (p.Gln16Gln), rs1353903423, gnomAD 11-102110896-A-G, CADD 12.00
- G17E (p.Gly17Glu), TOPMed rs1036138787, gnomAD rs1036138787, REVEL 0.10, CADD 23.00, Uncertain significance, not specified
- G17R (p.Gly17Arg), ExAC rs765528842, gnomAD rs765528842, REVEL 0.04, CADD 23.20
- G17V (p.Gly17Val), rs1036138787, ClinGen CA382490517, ClinVar RCV004485791, REVEL 0.08, CADD 23.10, Uncertain significance, not specified
- G17W (p.Gly17Trp), gnomAD 11-102110897-G-T, REVEL 0.12, CADD 25.70
- G17G (p.Gly17Gly), rs1942852479, gnomAD 11-102110899-G-A, CADD 13.90
- Q18L (p.Gln18Leu), TOPMed rs1391541668, REVEL 0.04, CADD 23.10
- Q18R (p.Gln18Arg), TOPMed rs1391541668, REVEL 0.05, CADD 17.90
- Q18E (p.Gln18Glu), gnomAD 11-102110900-C-G, REVEL 0.09, CADD 21.30
- Q18K (p.Gln18Lys), gnomAD 11-102110900-C-A, REVEL 0.08, CADD 17.80
- Q18* (p.Gln18Ter), gnomAD 11-102110900-C-T, CADD 35.00
- Q18P (p.Gln18Pro), gnomAD 11-102110901-A-C, REVEL 0.09, CADD 23.00
- Q18H (p.Gln18His), gnomAD 11-102110902-G-T, REVEL 0.09, CADD 23.90
- Q18Q (p.Gln18Gln), gnomAD 11-102110902-G-A, CADD 12.20
- P19L (p.Pro19Leu), TOPMed rs1415100005, gnomAD rs1415100005, REVEL 0.03, CADD 22.30
- P19Q (p.Pro19Gln), TOPMed rs1415100005, gnomAD rs1415100005, REVEL 0.03, CADD 21.70
- P19R (p.Pro19Arg), TOPMed rs1415100005, gnomAD rs1415100005, REVEL 0.02, CADD 21.90
- P19S (p.Pro19Ser), gnomAD rs1402910700, REVEL 0.06, CADD 20.90, Uncertain significance, not specified
- P19T (p.Pro19Thr), gnomAD rs1402910700, REVEL 0.06, CADD 20.00, Uncertain significance
- p.Pro19 Gln27del, rs1942852218, gnomAD 11-102110893-CCAA, CADD 18.30
- P19P (p.Pro19Pro), rs937455182, gnomAD 11-102110905-G-A, CADD 12.80
- P20L (p.Pro20Leu), TOPMed rs1942853316, REVEL 0.05, CADD 17.50
- P20T (p.Pro20Thr), cosmic curated COSV99176, REVEL 0.04, CADD 14.60
- P20S (p.Pro20Ser), gnomAD 11-102110906-C-T, REVEL 0.04, CADD 15.00
- P20A (p.Pro20Ala), gnomAD 11-102110906-C-G, REVEL 0.04, CADD 13.10
- P20H (p.Pro20His), gnomAD 11-102110907-C-A, REVEL 0.08, CADD 17.60
- P20P (p.Pro20Pro), gnomAD 11-102110908-T-C, CADD 9.39
- S21L (p.Ser21Leu), rs990765765, ClinGen CA228282923, ClinVar RCV003405035, TOPMed rs990765765, REVEL 0.07, CADD 22.20, Uncertain significance, not specified
- S21R (p.Ser21Arg), gnomAD 11-102110907-CT-C, CADD 13.80
- S21P (p.Ser21Pro), gnomAD 11-102110909-T-C, REVEL 0.07, CADD 19.30
- S21T (p.Ser21Thr), gnomAD 11-102110909-T-A, REVEL 0.03, CADD 16.80
- S21* (p.Ser21Ter), gnomAD 11-102110910-C-A, CADD 35.00
- S21W (p.Ser21Trp), gnomAD 11-102110910-C-G, REVEL 0.08, CADD 22.50
- S21S (p.Ser21Ser), gnomAD 11-102110911-G-T, CADD 9.01
- Q22K (p.Gln22Lys), gnomAD 11-102110912-C-A, REVEL 0.06, CADD 14.40
- Q22E (p.Gln22Glu), gnomAD 11-102110912-C-G, REVEL 0.08, CADD 13.70
- Q22* (p.Gln22Ter), gnomAD 11-102110912-C-T, CADD 34.00
- Q22R (p.Gln22Arg), gnomAD 11-102110913-A-G, REVEL 0.06, CADD 15.40
- Q22P (p.Gln22Pro), gnomAD 11-102110913-A-C, REVEL 0.05, CADD 16.20
- Q22H (p.Gln22His), gnomAD 11-102110914-G-T, REVEL 0.07, CADD 20.00
- Q22Q (p.Gln22Gln), rs1289245777, gnomAD 11-102110914-G-A, CADD 8.92
- P23A (p.Pro23Ala), TOPMed rs1465441942, gnomAD rs1465441942, REVEL 0.03, CADD 10.70
- P23S (p.Pro23Ser), TOPMed rs1465441942, gnomAD rs1465441942, REVEL 0.03, CADD 12.90
- P23T (p.Pro23Thr), cosmic curated COSV56776, REVEL 0.04, CADD 12.70
- P23H (p.Pro23His), gnomAD 11-102110916-C-A, REVEL 0.03, CADD 16.10
- P23R (p.Pro23Arg), gnomAD 11-102110916-C-G, REVEL 0.03, CADD 16.40
- P23P (p.Pro23Pro), gnomAD 11-102110917-C-T, CADD 9.44
- P24A (p.Pro24Ala), cosmic curated COSV56779, REVEL 0.05, CADD 8.88
- P24L (p.Pro24Leu), TOPMed rs1395090279, gnomAD rs1395090279, REVEL 0.06, CADD 18.20
- P24R (p.Pro24Arg), gnomAD 11-102110914-GC-G, CADD 20.80
- P24T (p.Pro24Thr), gnomAD 11-102110918-C-A, REVEL 0.03, CADD 13.30
- P24Q (p.Pro24Gln), gnomAD 11-102110919-C-A, REVEL 0.11, CADD 18.00
- P24P (p.Pro24Pro), rs1942854498, gnomAD 11-102110920-G-C, CADD 8.66
- Q25P (p.Gln25Pro), gnomAD rs1222068805, REVEL 0.07, CADD 17.60
- Q25A (p.Gln25Ala), gnomAD 11-102110914-G-GC, CADD 23.60
- Q25R (p.Gln25Arg), gnomAD 11-102110920-GC-G, CADD 23.50
- Q25K (p.Gln25Lys), gnomAD 11-102110921-C-A, REVEL 0.06, CADD 15.40
- Q25* (p.Gln25Ter), gnomAD 11-102110921-C-T, CADD 35.00
- Q25L (p.Gln25Leu), gnomAD 11-102110922-A-T, REVEL 0.04, CADD 18.90
- Q25Q (p.Gln25Gln), gnomAD 11-102110923-G-A, CADD 8.91
- Q25H (p.Gln25His), gnomAD 11-102110923-G-T, REVEL 0.06, CADD 16.20
- G26E (p.Gly26Glu), gnomAD rs1188136705, REVEL 0.07, CADD 18.40
- G26R (p.Gly26Arg), cosmic curated COSV99176, TOPMed rs1277114008, gnomAD rs1277114008, REVEL 0.08, CADD 19.70
- G26W (p.Gly26Trp), gnomAD 11-102110924-G-T, REVEL 0.07, CADD 23.00
- G26G (p.Gly26Gly), gnomAD 11-102110926-G-T, CADD 10.60
- Q27H (p.Gln27His), cosmic curated COSV56776, TOPMed rs914654817, gnomAD rs914654817, REVEL 0.03, CADD 16.30
- Q27A (p.Gln27Ala), gnomAD 11-102110922-A-AG, CADD 23.50
- Q27* (p.Gln27Ter), gnomAD 11-102110927-C-T, CADD 35.00
- Q27K (p.Gln27Lys), gnomAD 11-102110927-C-A, REVEL 0.05, CADD 15.70
- Q27R (p.Gln27Arg), gnomAD 11-102110928-A-G, REVEL 0.04, CADD 17.20
- Q27Q (p.Gln27Gln), rs914654817, gnomAD 11-102110929-G-A, CADD 9.87
- G28R (p.Gly28Arg), TOPMed rs1942855577, gnomAD rs1942855577, REVEL 0.08, CADD 17.20
- G28S (p.Gly28Ser), TOPMed rs1942855577, gnomAD rs1942855577, REVEL 0.07, CADD 18.90
- G28V (p.Gly28Val), Ensembl rs1942855756, REVEL 0.04, CADD 16.90
- G28C (p.Gly28Cys), gnomAD 11-102110930-G-T, REVEL 0.06, CADD 21.90
- G28D (p.Gly28Asp), gnomAD 11-102110931-G-A, REVEL 0.05, CADD 17.00
- G28G (p.Gly28Gly), gnomAD 11-102110932-C-T, CADD 12.70
- P29Q (p.Pro29Gln), rs2496404823, ClinGen CA382490597, ClinVar RCV004485793, REVEL 0.07, CADD 17.10, Uncertain significance, not specified
- P29S (p.Pro29Ser), Ensembl rs1301809602, REVEL 0.04, CADD 19.80
- P29T (p.Pro29Thr), gnomAD 11-102110933-C-A, REVEL 0.03, CADD 19.20
- P29L (p.Pro29Leu), gnomAD 11-102110934-C-T, REVEL 0.07, CADD 17.40
- P29R (p.Pro29Arg), gnomAD 11-102110934-C-G, REVEL 0.07, CADD 17.20
- P29P (p.Pro29Pro), rs1942856221, gnomAD 11-102110935-G-A, CADD 10.20
- P30T (p.Pro30Thr), gnomAD 11-102110936-C-A, REVEL 0.04, CADD 17.00
- P30S (p.Pro30Ser), gnomAD 11-102110936-C-T, REVEL 0.05, CADD 17.60
- P30L (p.Pro30Leu), gnomAD 11-102110937-C-T, REVEL 0.04, CADD 21.20
Public YAP1 analysis runs
- YAP1 analysis run — YAP1 (1,002 variants) — completed 2026-08-19