ARID2 (Q68CP9) variants and mutations
ARID2 (also known as Q68CP9) is a human protein-coding gene encoding an AT-rich interactive domain-containing protein 2 protein. It contributes DNA targeting and regulatory specificity to PBAF chromatin-remodeling complexes. Somatic loss-of-function alterations occur in melanoma, liver cancer, and other tumors, while germline variants can cause a Coffin-Siris-spectrum neurodevelopmental disorder. This analysis covers 7,631 ARID2 variants and mutations. Of these, 34% have computational variant effect predictions. Disease context includes Coffin-Siris syndrome 6, hepatocellular carcinoma, and melanoma. Example ARID2 variants include A2S, A2E, and N3H.
Variant analysis overview
- Gene: ARID2
- Protein: Q68CP9
- UniProt accession: Q68CP9
- Organism: Homo sapiens
- Variants analyzed: 7631
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 7,462 unspecified-consequence records; 49 missense variants; 104 synonymous variants; 2 stop-gained variants; 6 frameshift variants; 2 in-frame deletions; 4 splice-region variants; 1 in-frame insertions; 1 substitution
- Prediction scores: 2,567 variants have prediction scores (34% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Coffin-Siris syndrome 6, hepatocellular carcinoma, melanoma, Coffin-Siris syndrome, hereditary disease, neurodegenerative disease, cutaneous melanoma, cutaneous squamous cell carcinoma, neurodevelopmental disorder, medulloblastoma, esophageal cancer, atrial fibrillation.
Protein structure and variant hotspots
- Protein features: 1 domains; 10 post-translational modification sites.
- Structural context: 313 variants have structural context.
- PTM context: 33 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 ARID2 variants
Examples include A2S, A2E, N3H, N3N, N3K, S4S, T5M, T5R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), Ensembl rs2137958638, MetaLR 0.05, MetaSVM -1.08
- A2E (p.Ala2Glu), gnomAD 12-45729841-C-A, REVEL 0.15, MetaLR 0.05
- N3H (p.Asn3His), rs868029449, ClinGen CA236966917, ClinVar RCV001332970, gnomAD rs868029449, REVEL 0.11, MetaLR 0.10, Uncertain significance, Coffin-Siris syndrome 6
- N3N (p.Asn3Asn), rs1940937408, gnomAD 12-45729845-C-T, CADD 11.20
- N3K (p.Asn3Lys), gnomAD 12-45729845-C-A, REVEL 0.10, MetaLR 0.05
- S4S (p.Ser4Ser), rs781723038, gnomAD 12-45729848-G-T, CADD 12.30
- T5M (p.Thr5Met), ESP rs374143008, ExAC rs374143008, TOPMed rs374143008, gnomAD rs374143008, REVEL 0.20, MetaLR 0.12, Uncertain significance, not provided
- T5R (p.Thr5Arg), gnomAD 12-45729850-C-G, REVEL 0.21, MetaLR 0.12
- G6A (p.Gly6Ala), TOPMed rs1315009829, gnomAD rs1315009829
- G6E (p.Gly6Glu), TOPMed rs1315009829, gnomAD rs1315009829, REVEL 0.21, MetaLR 0.13
- G6R (p.Gly6Arg), rs2137958679, Ensembl rs2137958679, ClinGen CA384608920, ClinVar RCV004547141, REVEL 0.20, MetaLR 0.13, Uncertain significance, not provided
- G6W (p.Gly6Trp), gnomAD 12-45729852-G-T, REVEL 0.33, MetaLR 0.13
- G6G (p.Gly6Gly), rs574811185, gnomAD 12-45729854-G-A, CADD 12.40
- K7N (p.Lys7Asn), TOPMed rs1282124456, gnomAD rs1282124456, MetaLR 0.10, MetaSVM -1.01
- K7R (p.Lys7Arg), TOPMed rs1940937873, REVEL 0.09, MetaLR 0.11
- K7E (p.Lys7Glu), gnomAD 12-45729855-A-G, REVEL 0.10, MetaLR 0.11
- K7K (p.Lys7Lys), rs1282124456, gnomAD 12-45729857-G-A, CADD 11.00
- A8S (p.Ala8Ser), rs1374980785, ClinGen CA384608934, ClinVar RCV003397559, TOPMed rs1374980785, REVEL 0.05, MetaLR 0.03, Uncertain significance, ARID2-related disorder
- A8T (p.Ala8Thr), TOPMed rs1374980785, MetaLR 0.03, MetaSVM -1.06, Uncertain significance
- A8V (p.Ala8Val), Ensembl rs2137958721, REVEL 0.02, MetaLR 0.03
- A8P (p.Ala8Pro), gnomAD 12-45729858-G-C, REVEL 0.04, MetaLR 0.03
- A8E (p.Ala8Glu), gnomAD 12-45729859-C-A, REVEL 0.02, MetaLR 0.03
- A8A (p.Ala8Ala), rs542215365, gnomAD 12-45729860-G-A, CADD 13.10
- P9L (p.Pro9Leu), gnomAD 12-45729862-C-T, REVEL 0.03, MetaLR 0.03
- P10L (p.Pro10Leu), TOPMed rs1284913319, gnomAD rs1284913319, REVEL 0.08, MetaLR 0.07
- P10Q (p.Pro10Gln), TOPMed rs1284913319, gnomAD rs1284913319, MetaLR 0.10, MetaSVM -0.99
- P10S (p.Pro10Ser), 1000Genomes rs560068535, ExAC rs560068535, TOPMed rs560068535, gnomAD rs560068535, REVEL 0.02, MetaLR 0.07, Likely benign
- P10T (p.Pro10Thr), rs560068535, ClinGen CA156942, ClinVar RCV000120070, ClinVar RCV000930091, REVEL 0.05, MetaLR 0.07, Likely benign, not provided
- P10P (p.Pro10Pro), rs1316261380, gnomAD 12-45729866-G-A, CADD 13.10
- D11A (p.Asp11Ala), ExAC rs781611431, TOPMed rs781611431, gnomAD rs781611431, REVEL 0.12, MetaLR 0.11
- D11G (p.Asp11Gly), ExAC rs781611431, TOPMed rs781611431, gnomAD rs781611431, REVEL 0.14, MetaLR 0.12
- D11H (p.Asp11His), Ensembl rs1167789611, REVEL 0.20, MetaLR 0.14
- D11N (p.Asp11Asn), gnomAD 12-45729867-G-A, REVEL 0.16, MetaLR 0.12
- D11D (p.Asp11Asp), rs1266927346, gnomAD 12-45729869-C-T, CADD 11.70
- D11E (p.Asp11Glu), gnomAD 12-45729869-C-A, REVEL 0.09, MetaLR 0.04
- E12A (p.Glu12Ala), TOPMed rs897357659, gnomAD rs897357659
- E12G (p.Glu12Gly), TOPMed rs897357659, gnomAD rs897357659, MetaLR 0.05, MetaSVM -1.09, Likely benign, Inborn genetic diseases
- E12K (p.Glu12Lys), gnomAD rs1490903912, REVEL 0.06, MetaLR 0.04
- E12* (p.Glu12Ter), gnomAD 12-45729870-G-T, CADD 35.00
- E12D (p.Glu12Asp), gnomAD 12-45729872-G-T, REVEL 0.03, MetaLR 0.04
- E12E (p.Glu12Glu), rs768673828, gnomAD 12-45729872-G-A, CADD 11.60
- R13Q (p.Arg13Gln), Ensembl rs1940940278
- R13W (p.Arg13Trp), Ensembl rs2137958806, MetaLR 0.33, MetaSVM -0.39
- R13R (p.Arg13Arg), rs2137958824, gnomAD 12-45729875-G-A, CADD 13.70
- R14K (p.Arg14Lys), TOPMed rs1479528154, gnomAD rs1479528154, REVEL 0.26, MetaLR 0.29
- K15Q (p.Lys15Gln), ExAC rs774482788, TOPMed rs774482788, gnomAD rs774482788, REVEL 0.21, MetaLR 0.31
- K15R (p.Lys15Arg), Ensembl rs2137958846, MetaLR 0.31, MetaSVM -0.62
- K15K (p.Lys15Lys), gnomAD 12-45729881-G-A, CADD 12.50
- G16A (p.Gly16Ala), gnomAD rs1369471297, REVEL 0.22, MetaLR 0.26
- G16R (p.Gly16Arg), Ensembl rs2137958852, MetaLR 0.15, MetaSVM -0.94, Uncertain significance, Inborn genetic diseases
- G16E (p.Gly16Glu), gnomAD 12-45729883-G-A, REVEL 0.36, MetaLR 0.16
- L17F (p.Leu17Phe), TOPMed rs1418993336, gnomAD rs1418993336, REVEL 0.23, MetaLR 0.27
- L17I (p.Leu17Ile), TOPMed rs1418993336, gnomAD rs1418993336
- L17V (p.Leu17Val), TOPMed rs1418993336, gnomAD rs1418993336, MetaLR 0.18, MetaSVM -0.89
- L17L (p.Leu17Leu), gnomAD 12-45729887-C-A, CADD 15.50
- A18T (p.Ala18Thr), Ensembl rs2137958871, REVEL 0.19, MetaLR 0.26
- L20L (p.Leu20Leu), gnomAD 12-45729894-C-T, CADD 14.00
- D21V (p.Asp21Val), Ensembl rs2137958881, MetaLR 0.35, MetaSVM -0.42
- D21Y (p.Asp21Tyr), ExAC rs760657887, gnomAD rs760657887, REVEL 0.43, MetaLR 0.43
- D21G (p.Asp21Gly), gnomAD 12-45729898-A-G, REVEL 0.35, MetaLR 0.35
- D21E (p.Asp21Glu), gnomAD 12-45729899-C-A, REVEL 0.21, MetaLR 0.23
- E22S (p.Glu22Ser), gnomAD 12-45729881-G-GGG, CADD 26.10
- E22D (p.Glu22Asp), gnomAD 12-45729902-G-T, REVEL 0.26, MetaLR 0.21
- L23M (p.Leu23Met), gnomAD 12-45729903-C-A, REVEL 0.63, MetaLR 0.67
- L23L (p.Leu23Leu), rs1351942237, gnomAD 12-45729905-G-A, CADD 12.90
- R24L (p.Arg24Leu), TOPMed rs994735646, gnomAD rs994735646, REVEL 0.39, MetaLR 0.29
- R24Q (p.Arg24Gln), TOPMed rs994735646, gnomAD rs994735646, REVEL 0.24, MetaLR 0.22
- R24W (p.Arg24Trp), rs2547601384, ClinGen CA384609034, ClinVar RCV003391755, REVEL 0.44, MetaLR 0.40, Uncertain significance, not provided
- R24del (p.Arg24del), gnomAD 12-45729904-TGCG-, CADD 20.80
- R24R (p.Arg24Arg), gnomAD 12-45729908-G-A, CADD 14.60
- Q25* (p.Gln25Ter), Ensembl rs2137958906
- Q25L (p.Gln25Leu), gnomAD rs1940941538, REVEL 0.32, MetaLR 0.28
- Q25K (p.Gln25Lys), gnomAD 12-45729909-C-A, REVEL 0.28, MetaLR 0.16
- Q25H (p.Gln25His), gnomAD 12-45729911-G-T, REVEL 0.23, MetaLR 0.31
- F26L (p.Phe26Leu), NCI-TCGA Cosmic COSV5760, NCI-TCGA Cosmic COSV5761, REVEL 0.67, MetaLR 0.47, Uncertain significance, not provided
- H27Y (p.His27Tyr), Ensembl rs2137958927, MetaLR 0.37, MetaSVM -0.29
- H27H (p.His27His), rs770809258, gnomAD 12-45729917-C-T, CADD 14.60
- H28Y (p.His28Tyr), ExAC rs776446572, gnomAD rs776446572, MetaLR 0.14, MetaSVM -0.91
- H28H (p.His28His), rs1411192582, gnomAD 12-45729920-C-T, CADD 19.30
- S29N (p.Ser29Asn), Ensembl rs2137958948, REVEL 0.24, MetaLR 0.33
- S29R (p.Ser29Arg), Ensembl rs2137958958, MetaLR 0.24, MetaSVM -0.71
- S29S (p.Ser29Ser), gnomAD 12-45729923-C-T, CADD 21.90
- R30T (p.Arg30Thr), rs995867385, ClinGen CA236966923, ClinVar RCV003887665, TOPMed rs995867385, REVEL 0.45, MetaLR 0.38, Uncertain significance, not provided
- R30K (p.Arg30Lys), gnomAD 12-45729925-G-A, REVEL 0.36, MetaLR 0.27
- G31=, rs1488076478, NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; low impact.
- G31R (p.Gly31Arg), ExAC rs759263837, gnomAD rs759263837, REVEL 0.64, MetaLR 0.48
- G31W (p.Gly31Trp), gnomAD 12-45729927-G-T, REVEL 0.69, MetaLR 0.51
- G31G (p.Gly31Gly), rs1488076478, gnomAD 12-45730044-G-A, CADD 16.30
- S32A (p.Ser32Ala), Ensembl rs868411783
- S32L (p.Ser32Leu), TOPMed rs1261085081, gnomAD rs1261085081, REVEL 0.34, MetaLR 0.28
- S32P (p.Ser32Pro), Ensembl rs868411783
- S32T (p.Ser32Thr), NCI-TCGA Cosmic COSV5760, Ensembl rs868411783, Variant assessed as somatic; moderate impact.
- S32W (p.Ser32Trp), TOPMed rs1261085081, gnomAD rs1261085081
- P33H (p.Pro33His), TOPMed rs1218275094
- P33L (p.Pro33Leu), TOPMed rs1218275094
- P33R (p.Pro33Arg), TOPMed rs1218275094
- F34L (p.Phe34Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- F34S (p.Phe34Ser), Ensembl rs2137959587, MetaLR 0.21, MetaSVM -0.87
- K35* (p.Lys35Ter), NCI-TCGA Cosmic COSV5760, Ensembl rs2137959592, CADD 35.00, Likely pathogenic
- K35R (p.Lys35Arg), gnomAD 12-45730055-A-G, REVEL 0.05, MetaLR 0.13
- K36E (p.Lys36Glu), Ensembl rs1940948110
- K36R (p.Lys36Arg), gnomAD 12-45730058-A-G, REVEL 0.24, MetaLR 0.21
- K36N (p.Lys36Asn), gnomAD 12-45730059-A-T, REVEL 0.25, MetaLR 0.30
- I37F (p.Ile37Phe), Ensembl rs2137959616
- I37L (p.Ile37Leu), Ensembl rs2137959616
- I37M (p.Ile37Met), TOPMed rs1030658647
- I37N (p.Ile37Asn), Ensembl rs2137959629
- I37S (p.Ile37Ser), rs2137959629, NCI-TCGA Cosmic COSV5760, ClinGen CA384609138, ClinVar RCV003152139, AlphaMissense 0.95, MetaLR 0.27, Uncertain significance, not provided
- I37I (p.Ile37Ile), rs1030658647, gnomAD 12-45730062-C-T, CADD 13.10
- P38A (p.Pro38Ala), Ensembl rs2137959647
- P38L (p.Pro38Leu), ExAC rs768151419, gnomAD rs768151419, REVEL 0.76, MetaLR 0.76
- P38S (p.Pro38Ser), NCI-TCGA Cosmic COSV5759, REVEL 0.74, MetaLR 0.74, Variant assessed as somatic; moderate impact.
- P38P (p.Pro38Pro), rs1177962366, gnomAD 12-45730065-T-A, CADD 12.90
- A39E (p.Ala39Glu), ESP rs139981084, ExAC rs139981084, TOPMed rs139981084, gnomAD rs139981084, REVEL 0.14, MetaLR 0.17
- A39P (p.Ala39Pro), ExAC rs751021716, TOPMed rs751021716, gnomAD rs751021716
- A39S (p.Ala39Ser), ExAC rs751021716, TOPMed rs751021716, gnomAD rs751021716, REVEL 0.09, MetaLR 0.14
- A39V (p.Ala39Val), gnomAD 12-45730067-C-T, REVEL 0.04, MetaLR 0.05
- A39A (p.Ala39Ala), rs766691475, gnomAD 12-45730068-G-T, CADD 13.20
- V40E (p.Val40Glu), Ensembl rs2137959696
- V40L (p.Val40Leu), Ensembl rs2137959689
- V40M (p.Val40Met), Ensembl rs2137959689, MetaLR 0.34, MetaSVM -0.40
- V40A (p.Val40Ala), gnomAD 12-45730070-T-C, REVEL 0.37, MetaLR 0.25
- V40V (p.Val40Val), rs201596354, gnomAD 12-45730071-G-A, CADD 12.00
- G41D (p.Gly41Asp), Ensembl rs2137959716
- G41R (p.Gly41Arg), rs1940948860, ClinGen CA384609156, ClinVar RCV003141534, TOPMed rs1940948860, REVEL 0.48, MetaLR 0.46, Uncertain significance, Coffin-Siris syndrome 6
- G42E (p.Gly42Glu), rs2137959735, ClinGen CA384609164, ClinVar RCV002898437, Ensembl rs2137959735, REVEL 0.49, MetaLR 0.49, Uncertain significance, Inborn genetic diseases
- G42R (p.Gly42Arg), rs2137959723, Ensembl rs2137959723, ClinGen CA384609162, ClinVar RCV002284738, AlphaMissense 0.97, MetaLR 0.40, Uncertain significance, not provided
- G42W (p.Gly42Trp), Ensembl rs2137959723, MetaLR 0.53, MetaSVM 0.19
- G42G (p.Gly42Gly), gnomAD 12-45730077-G-A, CADD 12.80
- K43* (p.Lys43Ter), Ensembl rs2137959745
- K43R (p.Lys43Arg), Ensembl rs2137959751
- E44G (p.Glu44Gly), Ensembl rs2137959765, MetaLR 0.31, MetaSVM -0.61
- E44K (p.Glu44Lys), gnomAD 12-45730081-G-A, REVEL 0.25, MetaLR 0.32
- E44D (p.Glu44Asp), gnomAD 12-45730083-G-C, REVEL 0.17, MetaLR 0.21
- L45M (p.Leu45Met), ExAC rs755189381, gnomAD rs755189381, REVEL 0.48, MetaLR 0.54
- L45V (p.Leu45Val), ExAC rs755189381, gnomAD rs755189381, REVEL 0.25, MetaLR 0.27
- L45L (p.Leu45Leu), rs2137959783, gnomAD 12-45730086-G-A, CADD 13.80
- D46A (p.Asp46Ala), TOPMed rs1940949252
- D46E (p.Asp46Glu), Ensembl rs2137959802, REVEL 0.60, MetaLR 0.47
- D46H (p.Asp46His), TOPMed rs1940949155, REVEL 0.76, MetaLR 0.56
- D46N (p.Asp46Asn), TOPMed rs1940949155, MetaLR 0.38, MetaSVM -0.29
- L47F (p.Leu47Phe), gnomAD 12-45730090-C-T, REVEL 0.77, MetaLR 0.70
- L47P (p.Leu47Pro), gnomAD 12-45730091-T-C, REVEL 0.89, MetaLR 0.71
- H48D (p.His48Asp), Ensembl rs2137959811, Uncertain significance
- H48L (p.His48Leu), Ensembl rs2137959826
- H48P (p.His48Pro), Ensembl rs2137959826
- H48Y (p.His48Tyr), Ensembl rs2137959811, MetaLR 0.13, MetaSVM -0.97, Uncertain significance, Inborn genetic diseases
- H48H (p.His48His), rs1373206642, gnomAD 12-45730095-C-T, CADD 11.30
- G49R (p.Gly49Arg), TOPMed rs1039424180, REVEL 0.22, MetaLR 0.09
- G49S (p.Gly49Ser), TOPMed rs1039424180, MetaLR 0.10, MetaSVM -1.00, Uncertain significance, not provided
- L50L (p.Leu50Leu), gnomAD 12-45730101-C-G, CADD 12.10
- Y51C (p.Tyr51Cys), NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; moderate impact.
- Y51F (p.Tyr51Phe), Ensembl rs2137959852
- Y51N (p.Tyr51Asn), Ensembl rs2137959843, MetaLR 0.49, MetaSVM -0.07
- Y51Y (p.Tyr51Tyr), rs2137959858, gnomAD 12-45730104-C-T, CADD 11.70
- T52I (p.Thr52Ile), NCI-TCGA Cosmic COSV5760, Variant assessed as somatic; moderate impact.
- T52K (p.Thr52Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T52S (p.Thr52Ser), Ensembl rs2137959864, MetaLR 0.16, MetaSVM -0.98
- T52Q (p.Thr52Gln), gnomAD 12-45730102-TAC-T, CADD 25.70
- T52T (p.Thr52Thr), gnomAD 12-45730107-C-T, CADD 14.10
- R53G (p.Arg53Gly), gnomAD rs1338976862
- R53K (p.Arg53Lys), gnomAD rs1212941812, REVEL 0.27, MetaLR 0.19
- R53S (p.Arg53Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V54A (p.Val54Ala), NCI-TCGA Cosmic COSV5760, Variant assessed as somatic; moderate impact.
- V54D (p.Val54Asp), Ensembl rs2137959898
- V54I (p.Val54Ile), gnomAD rs1265019728, REVEL 0.55, MetaLR 0.56
- V54V (p.Val54Val), gnomAD 12-45730113-C-G, CADD 11.80
- T55I (p.Thr55Ile), Ensembl rs1940950053, Uncertain significance, not provided
- T55N (p.Thr55Asn), Ensembl rs1940950053, MetaLR 0.33, MetaSVM -0.39
- T55A (p.Thr55Ala), gnomAD 12-45730114-A-G, REVEL 0.18, MetaLR 0.26
- T56R (p.Thr56Arg), NCI-TCGA TCGA novel, MetaLR 0.26, MetaSVM -0.77, Variant assessed as somatic; high impact.
- T56S (p.Thr56Ser), gnomAD 12-45730118-C-G, REVEL 0.05, MetaLR 0.06
- L57* (p.Leu57Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L57F (p.Leu57Phe), TOPMed rs995317060, gnomAD rs995317060, REVEL 0.18, MetaLR 0.26
- L57I (p.Leu57Ile), Ensembl rs2137959932, MetaLR 0.30, MetaSVM -0.65
- L57S (p.Leu57Ser), ExAC rs748244027, TOPMed rs748244027, gnomAD rs748244027, REVEL 0.23, MetaLR 0.30
- G58S (p.Gly58Ser), Ensembl rs2137959953
- G58V (p.Gly58Val), Ensembl rs2137959958, MetaLR 0.77, MetaSVM 0.70
- G58G (p.Gly58Gly), gnomAD 12-45730125-C-A, CADD 12.60
- G59E (p.Gly59Glu), Ensembl rs2137959972
Public ARID2 analysis runs
- ARID2 analysis run — ARID2 (7,631 variants) — completed 2026-08-18