STAG2 (Cohesin subunit SA-2) variants and mutations
STAG2 (also known as Cohesin subunit SA-2) is a human protein-coding gene encoding a cohesin subunit SA-2 protein. It contributes to cohesin complexes that organize chromosomes, sister-chromatid cohesion, and three-dimensional gene regulation. Somatic loss-of-function mutations are common in myeloid neoplasms, bladder cancer, and other tumors, while germline variants can cause cohesinopathy-associated developmental disorders. This analysis covers 2,391 STAG2 variants and mutations. Of these, 33% have computational variant effect predictions. Disease context includes Mullegama-Klein-Martinez syndrome, alobar holoprosencephaly, and neurodegenerative disease. Example STAG2 variants include I2K, I2T, and I2V.
Variant analysis overview
- Gene: STAG2
- Protein: Cohesin subunit SA-2
- UniProt accession: Q8N3U4
- Organism: Homo sapiens
- Variants analyzed: 2391
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,228 unspecified-consequence records; 88 missense variants; 56 synonymous variants; 6 frameshift variants; 6 splice-region variants; 3 in-frame deletions; 3 stop-gained variants; 1 substitution
- Prediction scores: 781 variants have prediction scores (33% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Mullegama-Klein-Martinez syndrome, alobar holoprosencephaly, neurodegenerative disease, urinary bladder cancer, Ewing sarcoma, hereditary disease, acute myeloid leukemia, myelodysplastic syndrome, urinary bladder carcinoma, glioblastoma, Global developmental delay, microcephaly.
Protein structure and variant hotspots
- Protein features: 1 domains; 9 post-translational modification sites.
- Structural context: 149 variants have structural context.
- PTM context: 20 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 STAG2 variants
Examples include I2K, I2T, I2V, I2M, A3T, A3V, A3E, A3G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- I2K (p.Ile2Lys), cosmic curated COSV54365
- I2T (p.Ile2Thr), rs2056968861, ClinGen CA414271407, ClinVar RCV001332728, Ensembl rs2056968861, AlphaMissense 0.97, MetaLR 0.21, Uncertain significance, Mullegama-Klein-Martinez syndrome
- I2V (p.Ile2Val), Ensembl rs2148001384, REVEL 0.36, CADD 24.50
- I2M (p.Ile2Met), gnomAD X-124022633-A-G, REVEL 0.29, CADD 25.00
- A3T (p.Ala3Thr), gnomAD X-124022634-G-A, REVEL 0.20, CADD 24.20
- A3V (p.Ala3Val), gnomAD X-124022635-C-T, REVEL 0.24, CADD 25.90
- A3E (p.Ala3Glu), gnomAD X-124022635-C-A, REVEL 0.28, CADD 24.90
- A3G (p.Ala3Gly), gnomAD X-124022635-C-G, REVEL 0.21, CADD 25.00
- A3A (p.Ala3Ala), gnomAD X-124022636-A-G, CADD 13.00
- A4V (p.Ala4Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A4T (p.Ala4Thr), gnomAD X-124022637-G-A, REVEL 0.20, CADD 24.30
- A4D (p.Ala4Asp), gnomAD X-124022638-C-A, REVEL 0.14, CADD 23.60
- A4A (p.Ala4Ala), rs760530304, gnomAD X-124022639-T-C, CADD 13.10
- P5L (p.Pro5Leu), gnomAD X-124022641-C-T, REVEL 0.16, CADD 23.40
- P5Q (p.Pro5Gln), gnomAD X-124022641-C-A, REVEL 0.09, CADD 19.50
- P5P (p.Pro5Pro), gnomAD X-124022642-A-G, CADD 12.70
- E6* (p.Glu6Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E6D (p.Glu6Asp), cosmic curated COSV54352
- E6K (p.Glu6Lys), gnomAD X-124022643-G-A, REVEL 0.26, CADD 24.30
- E6E (p.Glu6Glu), gnomAD X-124022645-A-G, CADD 10.80
- I7V (p.Ile7Val), gnomAD X-124022646-A-G, REVEL 0.08, CADD 18.60
- I7M (p.Ile7Met), gnomAD X-124022648-A-G, REVEL 0.08, CADD 19.70
- P8Q (p.Pro8Gln), cosmic curated COSV54359, REVEL 0.14, CADD 19.60
- P8T (p.Pro8Thr), rs2523546164, ClinGen CA414271443, ClinVar RCV002576426, ClinVar RCV004725307, Conflicting interpretations, Mullegama-Klein-Martinez syndrome; Holoprosencephaly 13, X-linked; not provided
- P8S (p.Pro8Ser), gnomAD X-124022649-C-T, REVEL 0.06, CADD 17.60
- P8P (p.Pro8Pro), rs1363572853, gnomAD X-124022651-A-C, CADD 12.80
- T9A (p.Thr9Ala), gnomAD X-124022652-A-G, REVEL 0.03, CADD 18.40
- T9I (p.Thr9Ile), gnomAD X-124022653-C-T, REVEL 0.07, CADD 23.20
- T9N (p.Thr9Asn), gnomAD X-124022653-C-A, REVEL 0.05, CADD 20.70
- D10N (p.Asp10Asn), gnomAD X-124022655-G-A, REVEL 0.09, CADD 22.50
- F11L (p.Phe11Leu), gnomAD X-124022656-AT-A, CADD 26.80
- F11I (p.Phe11Ile), gnomAD X-124022658-T-A, REVEL 0.19, CADD 22.10
- F11S (p.Phe11Ser), gnomAD X-124022659-T-C, REVEL 0.25, CADD 24.30
- F11F (p.Phe11Phe), gnomAD X-124022660-T-C, CADD 12.20
- N12H (p.Asn12His), cosmic curated COSV54358
- N12S (p.Asn12Ser), rs899950130, ClinGen CA335276268, ClinVar RCV002601608, TOPMed rs899950130, REVEL 0.07, CADD 17.60, Uncertain significance, not provided
- N12Y (p.Asn12Tyr), NCI-TCGA Cosmic COSV5435, Variant assessed as somatic; moderate impact.
- N12N (p.Asn12Asn), gnomAD X-124022663-T-C, CADD 10.30
- L13I (p.Leu13Ile), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99494, REVEL 0.04, CADD 16.90, Variant assessed as somatic; moderate impact.
- L13P (p.Leu13Pro), gnomAD X-124022665-T-C, REVEL 0.11, CADD 23.50
- L13L (p.Leu13Leu), rs368486031, gnomAD X-124022666-A-G, CADD 8.38
- L14Q (p.Leu14Gln), rs2523546383, ClinGen CA414271502, ClinVar RCV003658979, Uncertain significance, not provided
- L14I (p.Leu14Ile), gnomAD X-124022667-C-A, REVEL 0.08, CADD 19.60
- L14P (p.Leu14Pro), gnomAD X-124022668-T-C, REVEL 0.08, CADD 22.20
- L14R (p.Leu14Arg), gnomAD X-124022668-T-G, REVEL 0.09, CADD 20.10
- Q15H (p.Gln15His), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99492, REVEL 0.06, CADD 31.00, Variant assessed as somatic; moderate impact.
- Q15R (p.Gln15Arg), ExAC rs776231686, gnomAD rs776231686, REVEL 0.13, CADD 22.90
- Q15K (p.Gln15Lys), gnomAD X-124022670-C-A, REVEL 0.15, CADD 23.60
- Q15Q (p.Gln15Gln), gnomAD X-124025840-G-A, CADD 21.50
- E16* (p.Glu16Ter), cosmic curated COSV54350
- E16G (p.Glu16Gly), cosmic curated COSV54359, REVEL 0.11, CADD 23.70
- E16K (p.Glu16Lys), cosmic curated COSV10725, REVEL 0.13, CADD 26.10
- E16Q (p.Glu16Gln), cosmic curated COSV10725
- E16E (p.Glu16Glu), gnomAD X-124025843-G-A, CADD 9.34
- S17* (p.Ser17Ter), cosmic curated COSV54369
- S17S (p.Ser17Ser), gnomAD X-124025846-A-G, CADD 12.20
- E18Q (p.Glu18Gln), gnomAD X-124025847-G-C, REVEL 0.07, CADD 22.80
- T19A (p.Thr19Ala), gnomAD X-124025850-A-G, REVEL 0.13, CADD 20.60
- T19K (p.Thr19Lys), gnomAD X-124025851-C-A, REVEL 0.11, CADD 22.90
- H20D (p.His20Asp), 1000Genomes rs188035163
- H20R (p.His20Arg), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, REVEL 0.06, CADD 19.00, Variant assessed as somatic; moderate impact.
- H20N (p.His20Asn), gnomAD X-124025853-C-A, REVEL 0.05, CADD 21.00
- H20Y (p.His20Tyr), gnomAD X-124025853-C-T, REVEL 0.12, CADD 23.40
- F21I (p.Phe21Ile), cosmic curated COSV10510, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F21V (p.Phe21Val), gnomAD rs1275593323, REVEL 0.18, CADD 21.50
- F21S (p.Phe21Ser), gnomAD X-124025857-T-C, REVEL 0.15, CADD 22.70
- F21F (p.Phe21Phe), gnomAD X-124025858-T-C, CADD 12.40
- S22F (p.Ser22Phe), NCI-TCGA TCGA novel, REVEL 0.07, CADD 22.70, Variant assessed as somatic; high impact.
- S22L (p.Ser22Leu), rs2148019067, gnomAD X-124025854-AT-A, CADD 24.60
- S22P (p.Ser22Pro), gnomAD X-124025859-T-C, REVEL 0.13, CADD 22.80
- S22S (p.Ser22Ser), rs201477761, gnomAD X-124025861-T-C, CADD 12.20
- S23F (p.Ser23Phe), cosmic curated COSV54376
- D24H (p.Asp24His), NCI-TCGA Cosmic COSV5436, cosmic curated COSV54363, Variant assessed as somatic; moderate impact.
- D24Y (p.Asp24Tyr), gnomAD X-124025865-G-T, REVEL 0.25, CADD 26.70
- D24N (p.Asp24Asn), gnomAD X-124025865-G-A, REVEL 0.12, CADD 23.40
- D24D (p.Asp24Asp), rs1214381957, gnomAD X-124025867-C-T, CADD 10.70
- D24E (p.Asp24Glu), gnomAD X-124025867-C-A, REVEL 0.10, CADD 17.60
- T25S (p.Thr25Ser), cosmic curated COSV54370
- T25I (p.Thr25Ile), gnomAD X-124025869-C-T, REVEL 0.17, CADD 23.50
- T25K (p.Thr25Lys), gnomAD X-124025869-C-A, REVEL 0.20, CADD 23.00
- T25T (p.Thr25Thr), rs1260949206, gnomAD X-124025870-A-G, CADD 10.60
- D26E (p.Asp26Glu), cosmic curated COSV54364, REVEL 0.12, CADD 15.90
- D26N (p.Asp26Asn), Ensembl rs1602909076, REVEL 0.14, CADD 24.10
- D26D (p.Asp26Asp), gnomAD X-124025873-T-C, CADD 9.50
- F27F (p.Phe27Phe), gnomAD X-124025876-T-C, CADD 12.60
- E28Q (p.Glu28Gln), cosmic curated COSV54371
- E28E (p.Glu28Glu), gnomAD X-124025879-A-G, CADD 10.60
- D29A (p.Asp29Ala), ExAC rs756567157, gnomAD rs756567157, REVEL 0.32, CADD 24.20
- D29G (p.Asp29Gly), ExAC rs756567157, gnomAD rs756567157, REVEL 0.32, CADD 23.60
- D29V (p.Asp29Val), gnomAD X-124025881-A-T, REVEL 0.35, CADD 24.20
- I30F (p.Ile30Phe), cosmic curated COSV54372
- I30T (p.Ile30Thr), TOPMed rs1179730186, gnomAD rs1179730186, REVEL 0.11, CADD 19.60
- I30I (p.Ile30Ile), rs1255264404, gnomAD X-124025885-C-T, CADD 6.95
- E31* (p.Glu31Ter), cosmic curated COSV54359
- E31K (p.Glu31Lys), cosmic curated COSV54370, gnomAD rs1251136516, REVEL 0.14, CADD 22.20
- E31D (p.Glu31Asp), gnomAD X-124025888-A-T, REVEL 0.05, CADD 19.00
- E31E (p.Glu31Glu), gnomAD X-124025888-A-G, CADD 12.70
- G32E (p.Gly32Glu), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99492, Variant assessed as somatic; moderate impact.
- G32G (p.Gly32Gly), rs367889026, gnomAD X-124025891-A-G, CADD 13.00
- K33R (p.Lys33Arg), rs2523584905, ClinGen CA414271686, ClinVar RCV002799456, Uncertain significance, Inborn genetic diseases
- N34K (p.Asn34Lys), rs2057078142, gnomAD X-124025890-G-GA, CADD 29.10
- p.Asn34 Gln35del, rs778053475, gnomAD X-124025892-AAAAA, CADD 17.60
- N34D (p.Asn34Asp), gnomAD X-124025895-A-G, REVEL 0.06, CADD 20.90
- Q35* (p.Gln35Ter), cosmic curated COSV10635
- Q35K (p.Gln35Lys), gnomAD X-124025898-C-A, REVEL 0.06, CADD 15.40
- Q35Q (p.Gln35Gln), gnomAD X-124025900-A-G, CADD 9.42
- K36K (p.Lys36Lys), rs2057078318, gnomAD X-124025903-G-A, CADD 9.61
- p.Gln37 Gly38del, rs1569506145, gnomAD X-124025903-GCAAG, CADD 19.10
- Q37* (p.Gln37Ter), gnomAD X-124025904-C-T, CADD 38.00
- Q37K (p.Gln37Lys), gnomAD X-124025904-C-A, REVEL 0.10, CADD 15.70
- Q37Q (p.Gln37Gln), rs1190058640, gnomAD X-124025906-A-G, CADD 10.70
- G38D (p.Gly38Asp), cosmic curated COSV10608
- G38G (p.Gly38Gly), rs2148019373, gnomAD X-124025909-C-A, CADD 9.48
- K39R (p.Lys39Arg), TOPMed rs950567395, REVEL 0.10, CADD 23.10
- K39T (p.Lys39Thr), gnomAD X-124025911-A-C, REVEL 0.13, CADD 24.10
- G40D (p.Gly40Asp), gnomAD X-124025914-G-A, REVEL 0.15, CADD 23.80
- G40G (p.Gly40Gly), gnomAD X-124025915-C-A, CADD 2.93
- K41R (p.Lys41Arg), gnomAD X-124025917-A-G, REVEL 0.12, CADD 22.70
- K41K (p.Lys41Lys), gnomAD X-124025918-A-G, CADD 14.10
- T42N (p.Thr42Asn), Ensembl rs2148061756
- T42A (p.Thr42Ala), gnomAD X-124030961-A-G, REVEL 0.05, CADD 18.70
- T42T (p.Thr42Thr), rs772218422, gnomAD X-124030963-T-A, CADD 15.30
- C43F (p.Cys43Phe), ExAC rs777752836, gnomAD rs777752836, REVEL 0.18, CADD 22.20
- C43Y (p.Cys43Tyr), ExAC rs777752836, gnomAD rs777752836
- C43C (p.Cys43Cys), rs1302246821, gnomAD X-124030966-T-C, CADD 11.90
- K44E (p.Lys44Glu), gnomAD rs1339518693
- K45N (p.Lys45Asn), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, Variant assessed as somatic; moderate impact.
- G46A (p.Gly46Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G46D (p.Gly46Asp), Ensembl rs2148061890, REVEL 0.28, CADD 23.30
- G46S (p.Gly46Ser), cosmic curated COSV54368, REVEL 0.29, CADD 23.40
- G46R (p.Gly46Arg), gnomAD X-124030966-T-TA, CADD 26.60
- G46G (p.Gly46Gly), gnomAD X-124030975-C-A, CADD 10.40
- K47Q (p.Lys47Gln), gnomAD rs1348108191, REVEL 0.12, CADD 23.50, Uncertain significance, Inborn genetic diseases
- K47R (p.Lys47Arg), gnomAD X-124030977-A-G, REVEL 0.12, CADD 18.40
- K48R (p.Lys48Arg), rs745799850, ClinGen CA10508563, ClinVar RCV002601444, ExAC rs745799850, REVEL 0.16, CADD 22.70, Uncertain significance, not provided
- K48K (p.Lys48Lys), rs927566661, gnomAD X-124030981-G-A, CADD 7.81
- G49C (p.Gly49Cys), rs1053797512, ClinGen CA414272198, ClinVar RCV002943339, AlphaMissense 0.66, MetaLR 0.10, Uncertain significance, not provided
- G49R (p.Gly49Arg), TOPMed rs1053797512
- G49S (p.Gly49Ser), TOPMed rs1053797512
- P50L (p.Pro50Leu), rs2057315917, ClinGen CA414272213, ClinVar RCV003439755, REVEL 0.05, CADD 20.70, Uncertain significance, not provided
- P50Q (p.Pro50Gln), Ensembl rs2057315917
- P50S (p.Pro50Ser), cosmic curated COSV10725
- A51E (p.Ala51Glu), gnomAD rs1436980550, REVEL 0.05, CADD 14.40
- A51G (p.Ala51Gly), rs1436980550, ClinGen CA414272222, ClinVar RCV003726383, REVEL 0.09, CADD 11.50, Uncertain significance, not provided
- A51T (p.Ala51Thr), Ensembl rs2148062005
- A51V (p.Ala51Val), gnomAD rs1436980550, REVEL 0.06, CADD 14.80
- E52K (p.Glu52Lys), gnomAD X-124030991-G-A, REVEL 0.13, CADD 22.60
- K53E (p.Lys53Glu), cosmic curated COSV99494
- K53N (p.Lys53Asn), Ensembl rs2148062072
- K53R (p.Lys53Arg), TOPMed rs1328419748, REVEL 0.16, CADD 22.10
- K53T (p.Lys53Thr), TOPMed rs1328419748
- G54C (p.Gly54Cys), cosmic curated COSV54358
- G54V (p.Gly54Val), cosmic curated COSV54375, TOPMed rs1205210487, gnomAD rs1205210487, REVEL 0.07, CADD 18.90, Uncertain significance, not provided
- G54G (p.Gly54Gly), rs2148062102, gnomAD X-124030999-C-A, CADD 7.01
- K55R (p.Lys55Arg), rs537432586, ClinGen CA335276892, cosmic curated COSV10608, ClinVar RCV002006820, REVEL 0.21, CADD 23.20, Uncertain significance, not provided
- G56C (p.Gly56Cys), cosmic curated COSV54375
- G56D (p.Gly56Asp), Ensembl rs2057316524
- G56S (p.Gly56Ser), rs761786663, ClinGen CA335276893, cosmic curated COSV54375, ClinVar RCV003441694, REVEL 0.04, CADD 4.66, Uncertain significance, not provided
- G57E (p.Gly57Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N58S (p.Asn58Ser), gnomAD X-124031010-A-G, REVEL 0.08, CADD 16.40
- N58N (p.Asn58Asn), rs769780930, gnomAD X-124031011-T-C, CADD 11.90
- G59R (p.Gly59Arg), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99492, Variant assessed as somatic; moderate impact.
- G59G (p.Gly59Gly), gnomAD X-124031014-A-T, CADD 9.53
- G60E (p.Gly60Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G60R (p.Gly60Arg), Ensembl rs2148062197
- G60G (p.Gly60Gly), rs775207470, gnomAD X-124031017-A-T, CADD 13.80
- G61E (p.Gly61Glu), cosmic curated COSV54372
- G61R (p.Gly61Arg), Ensembl rs878912187
- K62R (p.Lys62Arg), gnomAD X-124031022-A-G, REVEL 0.13, CADD 22.70
- P63H (p.Pro63His), NCI-TCGA Cosmic COSV5435, cosmic curated COSV54354, Variant assessed as somatic; moderate impact.
- P63L (p.Pro63Leu), TOPMed rs2057317187, REVEL 0.19, CADD 25.20
- P63P (p.Pro63Pro), gnomAD X-124031026-T-C, CADD 13.90
- P64F (p.Pro64Phe), cosmic curated COSV54358
- P64H (p.Pro64His), cosmic curated COSV10437
- P64L (p.Pro64Leu), cosmic curated COSV10725
- P64S (p.Pro64Ser), cosmic curated COSV54352, TOPMed rs2057317283
- P64T (p.Pro64Thr), cosmic curated COSV10510, NCI-TCGA Cosmic COSV5435, Variant assessed as somatic; moderate impact.
- P64del (p.Pro64del), rs2057317074, gnomAD X-124031023-ACCT-, CADD 17.70
- P67L (p.Pro67Leu), cosmic curated COSV54355, Ensembl rs2057317373, REVEL 0.08, CADD 19.50
- P67S (p.Pro67Ser), gnomAD X-124031036-C-T, REVEL 0.04, CADD 15.60
Public STAG2 analysis runs
- STAG2 analysis run — STAG2 (2,391 variants) — completed 2026-08-19