SUZ12 (Polycomb protein SUZ12) variants and mutations
SUZ12 (also known as Polycomb protein SUZ12) is a human protein-coding gene encoding a polycomb protein. Within Polycomb repressive complex 2, it helps establish H3K27 methylation-dependent gene silencing. Somatic loss or fusion events occur in several cancers, and germline pathogenic variants can cause overgrowth and neurodevelopmental syndromes. This analysis covers 886 SUZ12 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Imagawa-Matsumoto syndrome, hereditary disease, and prostate adenocarcinoma. Example SUZ12 variants include A2E, A2S, and A2V.
Variant analysis overview
- Gene: SUZ12
- Protein: Polycomb protein SUZ12
- UniProt accession: Q15022
- Organism: Homo sapiens
- Variants analyzed: 886
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 585 unspecified-consequence records; 185 missense variants; 82 synonymous variants; 11 frameshift variants; 9 stop-gained variants; 7 in-frame deletions; 4 in-frame insertions; 3 splice-region variants
- Prediction scores: 685 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Imagawa-Matsumoto syndrome, hereditary disease, prostate adenocarcinoma, viral infectious disease, melanoma, breast carcinoma, cancer, Weaver syndrome, endometrioid stromal sarcoma, hemangioblastoma, T-cell acute lymphoblastic leukemia, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 5 post-translational modification sites.
- PTM context: 7 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 SUZ12 variants
Examples include A2E, A2S, A2V, A2T, A2A, P3S, P3T, P3H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2E (p.Ala2Glu), TOPMed rs1394417218, gnomAD rs1394417218, REVEL 0.05, MetaLR 0.10
- A2S (p.Ala2Ser), TOPMed rs1905985424, REVEL 0.05, MetaLR 0.10
- A2V (p.Ala2Val), TOPMed rs1394417218, gnomAD rs1394417218, REVEL 0.04, MetaLR 0.08
- A2T (p.Ala2Thr), gnomAD 17-31937250-G-A, REVEL 0.06, MetaLR 0.09
- A2A (p.Ala2Ala), gnomAD 17-31937252-G-A, CADD 14.90
- P3S (p.Pro3Ser), Ensembl rs1905985813
- P3T (p.Pro3Thr), gnomAD 17-31937253-C-A, REVEL 0.08, MetaLR 0.11
- P3H (p.Pro3His), gnomAD 17-31937254-C-A, REVEL 0.11, MetaLR 0.10
- P3P (p.Pro3Pro), gnomAD 17-31937255-T-C, CADD 15.90
- Q4* (p.Gln4Ter), cosmic curated COSV59499, TOPMed rs1299892734, gnomAD rs1299892734, CADD 37.00
- Q4H (p.Gln4His), TOPMed rs887405183, gnomAD rs887405183, REVEL 0.16, MetaLR 0.09
- Q4R (p.Gln4Arg), gnomAD 17-31937257-A-G, REVEL 0.07, MetaLR 0.09
- Q4Q (p.Gln4Gln), rs887405183, gnomAD 17-31937258-G-A, CADD 13.30
- K5R (p.Lys5Arg), TOPMed rs1192634536, gnomAD rs1192634536, REVEL 0.06, MetaLR 0.10
- K5E (p.Lys5Glu), gnomAD 17-31937259-A-G, REVEL 0.06, MetaLR 0.10
- K5K (p.Lys5Lys), gnomAD 17-31937261-G-A, CADD 14.00
- K5N (p.Lys5Asn), gnomAD 17-31937261-G-T, REVEL 0.05, MetaLR 0.10
- H6D (p.His6Asp), rs1905986323, ClinGen CA399030262, ClinVar RCV002511423, AlphaMissense 0.23, MetaLR 0.28, Uncertain significance, not provided
- H6Q (p.His6Gln), rs760726816, ExAC rs760726816, TOPMed rs760726816, gnomAD rs760726816, REVEL 0.15, MetaLR 0.32, Uncertain significance, not provided
- H6Y (p.His6Tyr), Ensembl rs1905986323, REVEL 0.27, AlphaMissense 0.23
- H6N (p.His6Asn), gnomAD 17-31937262-C-A, REVEL 0.17, MetaLR 0.33
- H6P (p.His6Pro), gnomAD 17-31937263-A-C, REVEL 0.43, MetaLR 0.31
- H6L (p.His6Leu), gnomAD 17-31937263-A-T, REVEL 0.33, MetaLR 0.28
- H6R (p.His6Arg), gnomAD 17-31937263-A-G, REVEL 0.21, MetaLR 0.29
- H6H (p.His6His), rs760726816, gnomAD 17-31937264-C-T, CADD 13.80
- G7D (p.Gly7Asp), ExAC rs770347636, gnomAD rs770347636, REVEL 0.41, MetaLR 0.64
- G7V (p.Gly7Val), ExAC rs770347636, gnomAD rs770347636
- G7S (p.Gly7Ser), gnomAD 17-31937265-G-A, REVEL 0.28, MetaLR 0.52
- G7C (p.Gly7Cys), gnomAD 17-31937265-G-T, REVEL 0.37, MetaLR 0.74
- G7G (p.Gly7Gly), gnomAD 17-31937267-C-A, CADD 15.90
- G8S (p.Gly8Ser), Ensembl rs1905986735, REVEL 0.28, MetaLR 0.51
- G8V (p.Gly8Val), gnomAD 17-31937269-G-T, REVEL 0.37, MetaLR 0.63
- G8D (p.Gly8Asp), gnomAD 17-31937269-G-A, REVEL 0.34, MetaLR 0.61
- G8G (p.Gly8Gly), gnomAD 17-31937270-T-C, CADD 16.20
- G9R (p.Gly9Arg), gnomAD 17-31937271-G-A, REVEL 0.39, MetaLR 0.33
- G9W (p.Gly9Trp), gnomAD 17-31937271-G-T, REVEL 0.27, MetaLR 0.42
- G9E (p.Gly9Glu), gnomAD 17-31937272-G-A, REVEL 0.13, MetaLR 0.41
- G10R (p.Gly10Arg), Ensembl rs2142112607, REVEL 0.28, MetaLR 0.41
- G10V (p.Gly10Val), gnomAD rs1265386261, REVEL 0.34, MetaLR 0.41
- G10E (p.Gly10Glu), gnomAD 17-31937270-TG-T, CADD 32.00
- G10* (p.Gly10Ter), gnomAD 17-31937274-G-T, CADD 40.00
- G10G (p.Gly10Gly), rs1598140857, gnomAD 17-31937276-A-G, CADD 16.80
- G11W (p.Gly11Trp), gnomAD 17-31937277-G-T, REVEL 0.33, MetaLR 0.65
- G11R (p.Gly11Arg), gnomAD 17-31937277-G-A, REVEL 0.35, MetaLR 0.65
- G11V (p.Gly11Val), gnomAD 17-31937278-G-T, REVEL 0.39, MetaLR 0.67
- G12A (p.Gly12Ala), ExAC rs776325989, gnomAD rs776325989, REVEL 0.22, MetaLR 0.40
- G12C (p.Gly12Cys), gnomAD 17-31937280-G-T, REVEL 0.38, MetaLR 0.54
- G12S (p.Gly12Ser), gnomAD 17-31937280-G-A, REVEL 0.28, MetaLR 0.44
- G12D (p.Gly12Asp), gnomAD 17-31937281-G-A, REVEL 0.34, MetaLR 0.48
- G12V (p.Gly12Val), gnomAD 17-31937281-G-T, REVEL 0.41, MetaLR 0.44
- G12G (p.Gly12Gly), rs759212946, gnomAD 17-31937282-C-T, CADD 14.30
- G13S (p.Gly13Ser), gnomAD 17-31937283-G-A, REVEL 0.19, MetaLR 0.29
- G13D (p.Gly13Asp), gnomAD 17-31937284-G-A, REVEL 0.26, MetaLR 0.32
- G13G (p.Gly13Gly), gnomAD 17-31937285-C-A, CADD 14.70
- S14P (p.Ser14Pro), gnomAD rs1905987792
- S14* (p.Ser14Ter), gnomAD 17-31937287-C-A, CADD 37.00
- S14S (p.Ser14Ser), gnomAD 17-31937288-G-A, CADD 14.90
- G15V (p.Gly15Val), gnomAD 17-31937290-G-T, REVEL 0.32, MetaLR 0.45
- G15G (p.Gly15Gly), rs1238843146, gnomAD 17-31937291-G-A, CADD 14.60
- P16L (p.Pro16Leu), ExAC rs765010301, TOPMed rs765010301, gnomAD rs765010301, REVEL 0.27, MetaLR 0.35
- P16R (p.Pro16Arg), ExAC rs765010301, TOPMed rs765010301, gnomAD rs765010301, REVEL 0.27, MetaLR 0.35
- P16P (p.Pro16Pro), rs1429792906, gnomAD 17-31937294-C-T, CADD 15.50
- S17C (p.Ser17Cys), TOPMed rs1181343866, gnomAD rs1181343866, REVEL 0.33, MetaLR 0.18
- S17A (p.Ser17Ala), gnomAD 17-31937287-CG-C, CADD 32.00
- S17N (p.Ser17Asn), gnomAD 17-31937296-G-A, REVEL 0.30, MetaLR 0.27
- S17T (p.Ser17Thr), gnomAD 17-31937296-G-C, REVEL 0.24, MetaLR 0.28
- S17I (p.Ser17Ile), gnomAD 17-31937296-G-T, REVEL 0.27, MetaLR 0.27
- S17R (p.Ser17Arg), gnomAD 17-31937297-C-A, REVEL 0.31, MetaLR 0.20
- A18V (p.Ala18Val), 1000Genomes rs531045136, ExAC rs531045136, TOPMed rs531045136, gnomAD rs531045136, REVEL 0.18, MetaLR 0.25
- A18S (p.Ala18Ser), gnomAD 17-31937298-G-T, REVEL 0.23, MetaLR 0.19
- A18A (p.Ala18Ala), gnomAD 17-31937300-G-C, CADD 14.70
- G19W (p.Gly19Trp), Ensembl rs1905989323, REVEL 0.44, MetaLR 0.51
- G19V (p.Gly19Val), gnomAD 17-31937302-G-T, REVEL 0.32, MetaLR 0.56
- G19G (p.Gly19Gly), gnomAD 17-31937303-G-T, CADD 14.40
- S20P (p.Ser20Pro), Ensembl rs1905989490
- S20Y (p.Ser20Tyr), gnomAD 17-31937305-C-A, REVEL 0.17, MetaLR 0.26
- S20F (p.Ser20Phe), gnomAD 17-31937305-C-T, REVEL 0.18, MetaLR 0.27
- S20S (p.Ser20Ser), rs1376941123, gnomAD 17-31937306-C-T, CADD 14.90
- G21E (p.Gly21Glu), TOPMed rs1478319219, gnomAD rs1478319219, REVEL 0.42, MetaLR 0.34
- G21W (p.Gly21Trp), gnomAD 17-31937307-G-T, REVEL 0.48, MetaLR 0.46
- G21R (p.Gly21Arg), gnomAD 17-31937307-G-A, REVEL 0.30, MetaLR 0.30
- G21V (p.Gly21Val), gnomAD 17-31937308-G-T, REVEL 0.40, MetaLR 0.39
- G21G (p.Gly21Gly), gnomAD 17-31937309-G-A, CADD 14.50
- G22E (p.Gly22Glu), gnomAD 17-31937306-CG-C, CADD 29.90
- G22R (p.Gly22Arg), gnomAD 17-31937310-G-A, REVEL 0.37, MetaLR 0.34
- G22V (p.Gly22Val), gnomAD 17-31937311-G-T, REVEL 0.43, MetaLR 0.42
- G22G (p.Gly22Gly), rs1598140902, gnomAD 17-31937312-A-G, CADD 15.70
- G23S (p.Gly23Ser), gnomAD 17-31937313-G-A, REVEL 0.32, MetaLR 0.72
- G23C (p.Gly23Cys), gnomAD 17-31937313-G-T, REVEL 0.49, MetaLR 0.81
- G23V (p.Gly23Val), gnomAD 17-31937314-G-T, REVEL 0.42, MetaLR 0.74
- G23G (p.Gly23Gly), gnomAD 17-31937315-C-T, CADD 12.50
- G24D (p.Gly24Asp), gnomAD 17-31937317-G-A, REVEL 0.42, MetaLR 0.54
- G24V (p.Gly24Val), gnomAD 17-31937317-G-T, REVEL 0.41, MetaLR 0.54
- F25L (p.Phe25Leu), gnomAD rs1161554779, REVEL 0.19, MetaLR 0.30, Uncertain significance, not provided
- F25V (p.Phe25Val), gnomAD 17-31937319-T-G, REVEL 0.30, MetaLR 0.30
- F25S (p.Phe25Ser), gnomAD 17-31937320-T-C, REVEL 0.15, MetaLR 0.28
- F25F (p.Phe25Phe), rs1178278638, gnomAD 17-31937321-C-T, CADD 14.80
- G26R (p.Gly26Arg), cosmic curated COSV59500, TOPMed rs1421240953, gnomAD rs1421240953, REVEL 0.44, MetaLR 0.47
- G26W (p.Gly26Trp), TOPMed rs1421240953, gnomAD rs1421240953, REVEL 0.48, MetaLR 0.68
- G26V (p.Gly26Val), gnomAD 17-31937323-G-T, REVEL 0.50, MetaLR 0.65
- G26E (p.Gly26Glu), gnomAD 17-31937323-G-A, REVEL 0.42, MetaLR 0.55
- G26G (p.Gly26Gly), gnomAD 17-31937324-G-T, CADD 14.30
- G27D (p.Gly27Asp), TOPMed rs1464762189, gnomAD rs1464762189, REVEL 0.35, MetaLR 0.43
- G27V (p.Gly27Val), gnomAD 17-31937321-CG-C, CADD 32.00
- S28A (p.Ser28Ala), gnomAD rs1195824839, REVEL 0.12, MetaLR 0.37
- S28* (p.Ser28Ter), gnomAD 17-31937329-C-A, CADD 37.00
- S28L (p.Ser28Leu), gnomAD 17-31937329-C-T, REVEL 0.20, MetaLR 0.39
- S28S (p.Ser28Ser), gnomAD 17-31937330-G-T, CADD 14.00
- A29P (p.Ala29Pro), TOPMed rs1225019828, REVEL 0.20, MetaLR 0.24, Uncertain significance, Inborn genetic diseases
- A29T (p.Ala29Thr), gnomAD 17-31937331-G-A, REVEL 0.14, MetaLR 0.25
- A29S (p.Ala29Ser), gnomAD 17-31937331-G-T, REVEL 0.13, MetaLR 0.23
- A29G (p.Ala29Gly), gnomAD 17-31937332-C-G, REVEL 0.25, MetaLR 0.31
- A29V (p.Ala29Val), gnomAD 17-31937332-C-T, REVEL 0.22, MetaLR 0.25
- A29E (p.Ala29Glu), gnomAD 17-31937332-C-A, REVEL 0.29, MetaLR 0.28
- A29A (p.Ala29Ala), gnomAD 17-31937333-G-T, CADD 14.60
- A30V (p.Ala30Val), rs1284405136, ClinGen CA399030562, cosmic curated COSV59503, ClinVar RCV003215959, REVEL 0.13, MetaLR 0.37, Uncertain significance, Inborn genetic diseases
- p.Ala30dup, rs1905991672, gnomAD 17-31937328-T-TCG, CADD 20.90
- A30S (p.Ala30Ser), gnomAD 17-31937334-G-T, REVEL 0.17, MetaLR 0.41
- A30A (p.Ala30Ala), gnomAD 17-31937336-G-T, CADD 14.10
- V31A (p.Val31Ala), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, REVEL 0.20, MetaLR 0.38, Variant assessed as somatic; moderate impact.
- p.Val31 Ala34del, rs1364865405, gnomAD 17-31937328-TCGGC, CADD 20.80
- V31M (p.Val31Met), gnomAD 17-31937337-G-A, REVEL 0.24, MetaLR 0.43
- V31L (p.Val31Leu), gnomAD 17-31937337-G-T, REVEL 0.21, MetaLR 0.41
- V31V (p.Val31Val), gnomAD 17-31937339-G-T, CADD 12.40
- A32S (p.Ala32Ser), gnomAD 17-31937340-G-T, REVEL 0.26, MetaLR 0.31
- A32E (p.Ala32Glu), gnomAD 17-31937341-C-A, REVEL 0.17, MetaLR 0.25
- A32V (p.Ala32Val), gnomAD 17-31937341-C-T, REVEL 0.08, MetaLR 0.26
- A32A (p.Ala32Ala), gnomAD 17-31937342-G-T, CADD 13.60
- A33S (p.Ala33Ser), gnomAD rs1391996815, REVEL 0.15, MetaLR 0.27
- A33T (p.Ala33Thr), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; moderate impact.
- A33V (p.Ala33Val), rs997333005, ClinGen CA289421304, cosmic curated COSV10589, ClinVar RCV003992990, REVEL 0.31, MetaLR 0.29, Likely benign, not provided
- A33A (p.Ala33Ala), gnomAD 17-31937345-G-A, CADD 13.70
- A34G (p.Ala34Gly), rs561217691, ClinGen CA8489450, ClinVar RCV003288686, 1000Genomes rs561217691, REVEL 0.05, MetaLR 0.19, Likely benign, Inborn genetic diseases
- A34S (p.Ala34Ser), TOPMed rs1021200184, gnomAD rs1021200184, REVEL 0.12, MetaLR 0.25
- p.Ala34dup, gnomAD 17-31937338-T-TGG, CADD 18.70
- p.Ala34 Ala36del, rs1384625638, gnomAD 17-31937340-GCGGC, CADD 21.10
- A34V (p.Ala34Val), gnomAD 17-31937347-C-T, REVEL 0.10, MetaLR 0.24
- A34A (p.Ala34Ala), gnomAD 17-31937348-G-T, CADD 14.40
- T35A (p.Thr35Ala), TOPMed rs1224696424, gnomAD rs1224696424, REVEL 0.12, MetaLR 0.32
- T35M (p.Thr35Met), gnomAD rs1285528720, REVEL 0.32, MetaLR 0.39
- T35G (p.Thr35Gly), gnomAD 17-31937340-GCGGC, CADD 31.00
- T35T (p.Thr35Thr), gnomAD 17-31937351-G-T, CADD 12.10
- A36S (p.Ala36Ser), gnomAD 17-31937352-G-T, REVEL 0.16, MetaLR 0.30
- A36T (p.Ala36Thr), gnomAD 17-31937352-G-A, REVEL 0.21, MetaLR 0.29
- A36D (p.Ala36Asp), gnomAD 17-31937353-C-A, REVEL 0.34, MetaLR 0.32
- A36A (p.Ala36Ala), gnomAD 17-31937354-T-C, CADD 15.70
- S37L (p.Ser37Leu), rs1316496668, ClinGen CA399030675, cosmic curated COSV59504, ClinVar RCV003301826, REVEL 0.25, MetaLR 0.38, Uncertain significance, Inborn genetic diseases
- S37V (p.Ser37Val), gnomAD 17-31937353-C-CGG, CADD 28.00
- S37* (p.Ser37Ter), gnomAD 17-31937356-C-A, CADD 37.00
- S37S (p.Ser37Ser), rs1905995043, gnomAD 17-31937357-G-T, CADD 13.80
- G38D (p.Gly38Asp), gnomAD rs1252166484, REVEL 0.50, MetaLR 0.86
- G38S (p.Gly38Ser), gnomAD rs1218214351, REVEL 0.34, MetaLR 0.87
- G38C (p.Gly38Cys), gnomAD 17-31937358-G-T, REVEL 0.47, MetaLR 0.87
- G38V (p.Gly38Val), gnomAD 17-31937359-G-T, REVEL 0.37, MetaLR 0.87
- G38G (p.Gly38Gly), rs1455831223, gnomAD 17-31937360-C-T, CADD 14.90
- G39D (p.Gly39Asp), Ensembl rs866463572, REVEL 0.33, MetaLR 0.46
- G39S (p.Gly39Ser), cosmic curated COSV10589, TOPMed rs1001318910, gnomAD rs1001318910, REVEL 0.20, MetaLR 0.45
- G39C (p.Gly39Cys), gnomAD 17-31937361-G-T, REVEL 0.31, MetaLR 0.51
- G39V (p.Gly39Val), gnomAD 17-31937362-G-T, REVEL 0.17, MetaLR 0.45
- G39G (p.Gly39Gly), gnomAD 17-31937363-C-T, CADD 14.80
- K40I (p.Lys40Ile), TOPMed rs1032353170, gnomAD rs1032353170, Uncertain significance
- K40N (p.Lys40Asn), Ensembl rs1905996314
- K40R (p.Lys40Arg), rs1032353170, ClinGen CA289421321, ClinVar RCV004461259, TOPMed rs1032353170, REVEL 0.20, MetaLR 0.34, Uncertain significance, Inborn genetic diseases
- S41F (p.Ser41Phe), TOPMed rs959333610, REVEL 0.29, MetaLR 0.45
- S41P (p.Ser41Pro), gnomAD 17-31937367-T-C, REVEL 0.24, MetaLR 0.32
- S41T (p.Ser41Thr), gnomAD 17-31937367-T-A, REVEL 0.19, MetaLR 0.36
- S41Y (p.Ser41Tyr), gnomAD 17-31937368-C-A, REVEL 0.31, MetaLR 0.45
- S41S (p.Ser41Ser), rs752005012, gnomAD 17-31937369-C-G, CADD 14.40
- G42S (p.Gly42Ser), gnomAD 17-31937370-G-A, REVEL 0.20, MetaLR 0.43
- G42D (p.Gly42Asp), gnomAD 17-31937371-G-A, REVEL 0.42, MetaLR 0.55
- G42V (p.Gly42Val), gnomAD 17-31937371-G-T, REVEL 0.37, MetaLR 0.61
- G42G (p.Gly42Gly), gnomAD 17-31937372-C-T, CADD 12.90
- G43S (p.Gly43Ser), TOPMed rs1905996909
- G43C (p.Gly43Cys), gnomAD 17-31937373-G-T, REVEL 0.45, MetaLR 0.52
- G43V (p.Gly43Val), gnomAD 17-31937374-G-T, REVEL 0.41, MetaLR 0.44
- G43D (p.Gly43Asp), gnomAD 17-31937374-G-A, REVEL 0.33, MetaLR 0.41
- G43G (p.Gly43Gly), gnomAD 17-31937375-C-A, CADD 12.60
- G44E (p.Gly44Glu), TOPMed rs1359305761, gnomAD rs1359305761, REVEL 0.50, MetaLR 0.86
- G44R (p.Gly44Arg), gnomAD 17-31937376-G-A, REVEL 0.52, MetaLR 0.88
- G44W (p.Gly44Trp), gnomAD 17-31937376-G-T, REVEL 0.43, MetaLR 0.92
Public SUZ12 analysis runs
- SUZ12 analysis run — SUZ12 (886 variants) — completed 2026-08-19