SOX9 (Transcription factor SOX-9) variants and mutations
SOX9 (also known as Transcription factor SOX-9) is a human protein-coding gene encoding a transcription factor SOX-9 protein. It controls chondrocyte differentiation, cartilage formation, and testis development and also regulates multiple organ-specific developmental programs. Haploinsufficiency causes campomelic dysplasia, often with severe skeletal abnormalities and 46,XY sex reversal. This analysis covers 2,691 SOX9 variants and mutations. Of these, 40% have computational variant effect predictions. Disease context includes campomelic dysplasia, Pierre-Robin sequence, and neurodegenerative disease. Example SOX9 variants include N2D, N2K, and N2T.
Variant analysis overview
- Gene: SOX9
- Protein: Transcription factor SOX-9
- UniProt accession: P48436
- Organism: Homo sapiens
- Variants analyzed: 2691
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,458 unspecified-consequence records; 51 missense variants; 164 synonymous variants; 6 in-frame deletions; 3 stop-gained variants; 1 in-frame insertions; 3 frameshift variants; 1 splice-region variants; 4 substitution
- Prediction scores: 1,072 variants have prediction scores (40% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: campomelic dysplasia, Pierre-Robin sequence, neurodegenerative disease, colorectal adenocarcinoma, hereditary disease, connective tissue disorder, isolated Pierre-Robin syndrome, 46,XY complete gonadal dysgenesis, 46,XX testicular disorder of sex development, nodular goiter, colorectal cancer, dentures.
Protein structure and variant hotspots
- Protein features: 2 post-translational modification sites.
- PTM context: 12 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 SOX9 variants
Examples include N2D, N2K, N2T, N2Y, N2S, L3H, L3P, L3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- N2D (p.Asn2Asp), cosmic curated COSV99818, Ensembl rs2143236093
- N2K (p.Asn2Lys), gnomAD rs1479987082, REVEL 0.75, MetaLR 0.91
- N2T (p.Asn2Thr), Ensembl rs2143236104
- N2Y (p.Asn2Tyr), Ensembl rs2143236093
- N2S (p.Asn2Ser), gnomAD 17-72121396-A-G, REVEL 0.67, MetaLR 0.90
- L3H (p.Leu3His), Ensembl rs2143236114
- L3P (p.Leu3Pro), Ensembl rs2143236114
- L3L (p.Leu3Leu), rs746539387, gnomAD 17-72121400-C-G, CADD 14.10
- L4M (p.Leu4Met), NCI-TCGA TCGA novel, Ensembl rs2143236129, Variant assessed as somatic; moderate impact.
- L4V (p.Leu4Val), gnomAD 17-72121401-C-G, REVEL 0.68, MetaLR 0.92
- D5A (p.Asp5Ala), Ensembl rs2143236163, REVEL 0.81, MetaLR 0.96
- D5E (p.Asp5Glu), rs768210143, ClinGen CA8738859, ClinVar RCV002834196, ExAC rs768210143, REVEL 0.53, MetaLR 0.93, Uncertain significance, Camptomelic dysplasia
- D5G (p.Asp5Gly), Ensembl rs2143236163
- D5H (p.Asp5His), TOPMed rs1908084450, gnomAD rs1908084450, Uncertain significance
- D5N (p.Asp5Asn), TOPMed rs1908084450, gnomAD rs1908084450, REVEL 0.61, MetaLR 0.95, Uncertain significance, Inborn genetic diseases
- D5V (p.Asp5Val), Ensembl rs2143236163
- D5Y (p.Asp5Tyr), TOPMed rs1908084450, gnomAD rs1908084450, REVEL 0.87, MetaLR 0.96, Uncertain significance
- D5D (p.Asp5Asp), rs768210143, gnomAD 17-72121406-C-T, CADD 14.60
- P6A (p.Pro6Ala), TOPMed rs866679165, gnomAD rs866679165, REVEL 0.78, MetaLR 0.96, Likely benign
- P6H (p.Pro6His), cosmic curated COSV55428, Ensembl rs2143236201
- P6L (p.Pro6Leu), Ensembl rs2143236201, REVEL 0.85, MetaLR 0.96
- P6S (p.Pro6Ser), rs866679165, ClinGen CA293780901, ClinVar RCV002627868, ClinVar RCV002627869, REVEL 0.65, MetaLR 0.94, Conflicting interpretations, Inborn genetic diseases; not provided; Camptomelic dysplasia
- P6T (p.Pro6Thr), TOPMed rs866679165, gnomAD rs866679165, Likely benign
- P6P (p.Pro6Pro), rs780889240, gnomAD 17-72121409-C-T, CADD 15.10
- F7I (p.Phe7Ile), Ensembl rs2143236219
- F7L (p.Phe7Leu), NCI-TCGA TCGA novel, Ensembl rs2143236219, Variant assessed as somatic; moderate impact.
- M8I (p.Met8Ile), TOPMed rs1452893426, gnomAD rs1452893426, REVEL 0.41, MetaLR 0.84, Uncertain significance, Camptomelic dysplasia; Inborn genetic diseases
- M8K (p.Met8Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M8L (p.Met8Leu), TOPMed rs1221846522, REVEL 0.40, MetaLR 0.58
- K9* (p.Lys9Ter), Ensembl rs2143236265
- K9E (p.Lys9Glu), Ensembl rs2143236265
- K9M (p.Lys9Met), Ensembl rs2143236278
- K9N (p.Lys9Asn), ExAC rs747794183, gnomAD rs747794183
- K9K (p.Lys9Lys), rs747794183, gnomAD 17-72121418-G-A, CADD 14.20
- M10I (p.Met10Ile), Ensembl rs2143236315, REVEL 0.83, MetaLR 0.95
- M10K (p.Met10Lys), Ensembl rs2143236306
- M10L (p.Met10Leu), Ensembl rs2143236293
- M10R (p.Met10Arg), Ensembl rs2143236306
- M10T (p.Met10Thr), Ensembl rs2143236306, REVEL 0.83, MetaLR 0.95
- M10V (p.Met10Val), Ensembl rs2143236293
- T11A (p.Thr11Ala), cosmic curated COSV55423, TOPMed rs1287145712, Uncertain significance
- T11I (p.Thr11Ile), TOPMed rs1244512563, REVEL 0.74, MetaLR 0.93, Uncertain significance, not specified
- T11N (p.Thr11Asn), TOPMed rs1244512563
- T11P (p.Thr11Pro), TOPMed rs1287145712, REVEL 0.73, MetaLR 0.91, Uncertain significance, Inborn genetic diseases
- T11S (p.Thr11Ser), TOPMed rs1244512563, REVEL 0.44, MetaLR 0.83, Uncertain significance
- D12A (p.Asp12Ala), Ensembl rs2143236383
- D12E (p.Asp12Glu), Ensembl rs1908085553, REVEL 0.41, MetaLR 0.61
- D12G (p.Asp12Gly), Ensembl rs2143236383
- D12H (p.Asp12His), Ensembl rs2143236369
- D12N (p.Asp12Asn), Ensembl rs2143236369
- D12V (p.Asp12Val), Ensembl rs2143236383
- D12Y (p.Asp12Tyr), Ensembl rs2143236369
- D12D (p.Asp12Asp), rs1908085553, gnomAD 17-72121427-C-T, CADD 14.40
- E13* (p.Glu13Ter), TOPMed rs1478425968, gnomAD rs1478425968, CADD 37.00
- E13D (p.Glu13Asp), TOPMed rs1172992469, gnomAD rs1172992469, REVEL 0.50, MetaLR 0.94
- E13K (p.Glu13Lys), cosmic curated COSV55423, TOPMed rs1478425968, gnomAD rs1478425968, REVEL 0.76, MetaLR 0.96
- E13Q (p.Glu13Gln), TOPMed rs1478425968, gnomAD rs1478425968
- E13V (p.Glu13Val), Ensembl rs2143236423
- Q14* (p.Gln14Ter), cosmic curated COSV10874, Ensembl rs2143236435
- Q14E (p.Gln14Glu), Ensembl rs2143236435, REVEL 0.52, MetaLR 0.94
- Q14H (p.Gln14His), ExAC rs769605571, TOPMed rs769605571, gnomAD rs769605571, Benign
- Q14K (p.Gln14Lys), Ensembl rs2143236435, REVEL 0.59, MetaLR 0.95
- Q14L (p.Gln14Leu), Ensembl rs2143236451
- Q14R (p.Gln14Arg), cosmic curated COSV55427, Ensembl rs2143236451
- Q14Q (p.Gln14Gln), rs769605571, gnomAD 17-72121433-G-A, CADD 13.50
- E15D (p.Glu15Asp), Ensembl rs2143236487
- E15K (p.Glu15Lys), ExAC rs772903403, gnomAD rs772903403, REVEL 0.60, MetaLR 0.88
- E15Q (p.Glu15Gln), ExAC rs772903403, gnomAD rs772903403
- E15del (p.Glu15del), rs756571117, gnomAD 17-72121431-CAGG-, CADD 22.50
- E15* (p.Glu15Ter), gnomAD 17-72121434-G-T, CADD 38.00
- E15G (p.Glu15Gly), gnomAD 17-72121435-A-G, REVEL 0.57, MetaLR 0.87
- E15E (p.Glu15Glu), rs2143236487, gnomAD 17-72121436-G-A, CADD 14.00
- K16E (p.Lys16Glu), Ensembl rs2143236499
- K16M (p.Lys16Met), TOPMed rs1404583942, gnomAD rs1404583942, REVEL 0.78, MetaLR 0.96, Uncertain significance, Camptomelic dysplasia
- K16N (p.Lys16Asn), TOPMed rs1412757423, gnomAD rs1412757423, Likely benign
- K16R (p.Lys16Arg), TOPMed rs1404583942, gnomAD rs1404583942, REVEL 0.61, MetaLR 0.95
- K16T (p.Lys16Thr), NCI-TCGA TCGA novel, TOPMed rs1404583942, gnomAD rs1404583942, Variant assessed as somatic; moderate impact.
- K16K (p.Lys16Lys), rs1412757423, gnomAD 17-72121439-G-A, CADD 14.30
- G17C (p.Gly17Cys), Ensembl rs2143236526
- G17D (p.Gly17Asp), ExAC rs762942282, TOPMed rs762942282, gnomAD rs762942282
- G17V (p.Gly17Val), ExAC rs762942282, TOPMed rs762942282, gnomAD rs762942282, REVEL 0.45, MetaLR 0.80, Uncertain significance, Camptomelic dysplasia
- G17S (p.Gly17Ser), gnomAD 17-72121440-G-A, REVEL 0.36, MetaLR 0.72
- G17G (p.Gly17Gly), gnomAD 17-72121442-C-A, CADD 14.90
- L18M (p.Leu18Met), Ensembl rs2143236549
- L18P (p.Leu18Pro), rs770996719, ClinGen CA400865417, ClinVar RCV003605100, ExAC rs770996719, REVEL 0.50, MetaLR 0.90, Uncertain significance, Camptomelic dysplasia
- L18Q (p.Leu18Gln), ExAC rs770996719, TOPMed rs770996719, gnomAD rs770996719, Uncertain significance
- L18R (p.Leu18Arg), ExAC rs770996719, TOPMed rs770996719, gnomAD rs770996719, REVEL 0.45, MetaLR 0.89, Uncertain significance, Inborn genetic diseases
- L18V (p.Leu18Val), gnomAD 17-72121443-C-G, REVEL 0.33, MetaLR 0.82
- L18L (p.Leu18Leu), rs1351767351, gnomAD 17-72121445-G-T, CADD 13.70
- p.Leu18 Ser19insCysArg, gnomAD 17-72121445-G-GTG, CADD 21.60
- S19A (p.Ser19Ala), TOPMed rs1908086972, REVEL 0.60, MetaLR 0.95, Likely benign
- S19F (p.Ser19Phe), rs775652942, ClinGen CA8738867, ClinVar RCV002791628, ExAC rs775652942, REVEL 0.75, MetaLR 0.96, Uncertain significance, Camptomelic dysplasia
- S19P (p.Ser19Pro), TOPMed rs1908086972, REVEL 0.69, MetaLR 0.95, Likely benign
- S19T (p.Ser19Thr), rs1908086972, ClinGen CA400865418, ClinVar RCV002105827, TOPMed rs1908086972, REVEL 0.57, MetaLR 0.95, Likely benign, Camptomelic dysplasia
- S19C (p.Ser19Cys), gnomAD 17-72121447-C-G, REVEL 0.69, MetaLR 0.96
- S19S (p.Ser19Ser), rs2143236601, gnomAD 17-72121448-C-T, CADD 13.60
- G20A (p.Gly20Ala), rs1276160255, ClinGen CA400865427, ClinVar RCV001337649, gnomAD rs1276160255, REVEL 0.39, MetaLR 0.78, Uncertain significance, Camptomelic dysplasia
- G20C (p.Gly20Cys), Ensembl rs2143236607
- G20D (p.Gly20Asp), gnomAD rs1276160255, Uncertain significance
- G20R (p.Gly20Arg), Ensembl rs2143236607
- G20S (p.Gly20Ser), Ensembl rs2143236607
- G20V (p.Gly20Val), gnomAD rs1276160255, Uncertain significance
- G20G (p.Gly20Gly), rs1306437332, gnomAD 17-72121451-C-T, CADD 14.90
- A21G (p.Ala21Gly), Ensembl rs2143236661
- A21T (p.Ala21Thr), rs193920972, ClinGen CA174087, cosmic curated COSV55426, ClinVar RCV000148999, REVEL 0.61, MetaLR 0.94, Uncertain significance, Prostate cancer
- A21V (p.Ala21Val), gnomAD 17-72121453-C-T, REVEL 0.50, MetaLR 0.93
- P22H (p.Pro22His), ExAC rs760834344, gnomAD rs760834344
- P22L (p.Pro22Leu), cosmic curated COSV55422, ExAC rs760834344, gnomAD rs760834344
- P22R (p.Pro22Arg), ExAC rs760834344, gnomAD rs760834344, REVEL 0.54, MetaLR 0.64
- P22S (p.Pro22Ser), gnomAD rs1019580760, REVEL 0.43, MetaLR 0.53, Likely benign, Camptomelic dysplasia
- P22T (p.Pro22Thr), cosmic curated COSV99818, gnomAD rs1019580760
- P22A (p.Pro22Ala), gnomAD 17-72121454-CCCCA, CADD 32.00
- P22P (p.Pro22Pro), rs2143236710, gnomAD 17-72121457-C-G, CADD 15.50
- S23A (p.Ser23Ala), NCI-TCGA Cosmic COSV5542, Variant assessed as somatic; high impact.
- S23C (p.Ser23Cys), Ensembl rs2143236720
- S23G (p.Ser23Gly), Ensembl rs2143236720
- S23R (p.Ser23Arg), Ensembl rs900105206
- S23S (p.Ser23Ser), rs900105206, gnomAD 17-72121460-C-T, CADD 15.90
- P24H (p.Pro24His), Ensembl rs2143236766
- P24L (p.Pro24Leu), Ensembl rs2143236766, REVEL 0.54, MetaLR 0.71
- P24S (p.Pro24Ser), Ensembl rs2143236756
- P24T (p.Pro24Thr), cosmic curated COSV55429, Ensembl rs2143236756
- P24V (p.Pro24Val), gnomAD 17-72121459-GCCCC, CADD 32.00
- P24P (p.Pro24Pro), gnomAD 17-72121463-C-T, CADD 15.90
- T25I (p.Thr25Ile), Ensembl rs2143236788, REVEL 0.36, MetaLR 0.30
- T25N (p.Thr25Asn), Ensembl rs2143236788
- T25P (p.Thr25Pro), TOPMed rs1908087738
- T25S (p.Thr25Ser), TOPMed rs1908087738
- M26I (p.Met26Ile), gnomAD rs1482055922, REVEL 0.38, MetaLR 0.45
- M26K (p.Met26Lys), rs1908088001, ClinGen CA400865462, ClinVar RCV003062486, TOPMed rs1908088001, AlphaMissense 0.38, MetaLR 0.49, Uncertain significance, Camptomelic dysplasia
- M26L (p.Met26Leu), 1000Genomes rs575451633, ExAC rs575451633, TOPMed rs575451633, gnomAD rs575451633, Benign
- M26V (p.Met26Val), rs575451633, ClinGen CA8738869, cosmic curated COSV55425, ClinVar RCV001518396, REVEL 0.38, MetaLR 0.40, Benign, not provided; Camptomelic dysplasia
- M26R (p.Met26Arg), gnomAD 17-72121468-T-G, REVEL 0.62, MetaLR 0.51
- S27A (p.Ser27Ala), Ensembl rs2143236829
- S27C (p.Ser27Cys), TOPMed rs1664736339, Likely benign
- S27F (p.Ser27Phe), TOPMed rs1664736339, Likely benign
- S27P (p.Ser27Pro), Ensembl rs2143236829
- S27T (p.Ser27Thr), Ensembl rs2143236829
- S27Y (p.Ser27Tyr), rs1664736339, ClinGen CA400865471, ClinVar RCV003083510, TOPMed rs1664736339, AlphaMissense 0.77, MetaLR 0.75, Likely benign, Camptomelic dysplasia
- S27S (p.Ser27Ser), rs754070157, gnomAD 17-72121472-C-G, CADD 15.10
- E28* (p.Glu28Ter), cosmic curated COSV55422, Ensembl rs2143236858
- E28D (p.Glu28Asp), TOPMed rs1908088301, gnomAD rs1908088301, cosmic curated COSV55428
- E28G (p.Glu28Gly), Ensembl rs2143236867
- E28K (p.Glu28Lys), Ensembl rs2143236858
- E28Q (p.Glu28Gln), Ensembl rs2143236858
- E28V (p.Glu28Val), Ensembl rs2143236867
- E28L (p.Glu28Leu), gnomAD 17-72121471-C-CAT, CADD 31.00
- E28E (p.Glu28Glu), rs1908088301, gnomAD 17-72121475-G-A, CADD 13.10
- D29A (p.Asp29Ala), TOPMed rs1371768776
- D29E (p.Asp29Glu), NCI-TCGA TCGA novel, Ensembl rs2143236908, REVEL 0.29, MetaLR 0.34, Variant assessed as somatic; moderate impact.
- D29G (p.Asp29Gly), TOPMed rs1371768776
- D29H (p.Asp29His), Ensembl rs2143236883
- D29N (p.Asp29Asn), cosmic curated COSV10504, Ensembl rs2143236883
- D29V (p.Asp29Val), TOPMed rs1371768776
- D29Y (p.Asp29Tyr), Ensembl rs2143236883
- S30C (p.Ser30Cys), TOPMed rs1003847603, gnomAD rs1003847603
- S30F (p.Ser30Phe), TOPMed rs1003847603, gnomAD rs1003847603, REVEL 0.55, MetaLR 0.66, Uncertain significance, not provided
- S30P (p.Ser30Pro), Ensembl rs2143236918
- S30T (p.Ser30Thr), Ensembl rs2143236918
- S30Y (p.Ser30Tyr), TOPMed rs1003847603, gnomAD rs1003847603, REVEL 0.54, MetaLR 0.66
- S30S (p.Ser30Ser), rs2143236932, gnomAD 17-72121481-C-T, CADD 10.70
- A31E (p.Ala31Glu), Ensembl rs2143236953
- A31G (p.Ala31Gly), cosmic curated COSV55430, Ensembl rs2143236953
- A31P (p.Ala31Pro), TOPMed rs1257248748, gnomAD rs1257248748
- A31S (p.Ala31Ser), TOPMed rs1257248748, gnomAD rs1257248748, REVEL 0.28, MetaLR 0.19
- A31T (p.Ala31Thr), TOPMed rs1257248748, gnomAD rs1257248748, REVEL 0.37, MetaLR 0.44
- A31V (p.Ala31Val), NCI-TCGA Cosmic COSV5542, cosmic curated COSV55424, NCI-TCGA Cosmic COSV5543, Ensembl rs2143236953, Variant assessed as somatic; moderate impact.
- A31A (p.Ala31Ala), rs1488790677, gnomAD 17-72121484-G-T, CADD 12.80
- G32A (p.Gly32Ala), gnomAD rs1417947256
- G32D (p.Gly32Asp), gnomAD rs1417947256, REVEL 0.39, MetaLR 0.51
- G32R (p.Gly32Arg), TOPMed rs1196498041, gnomAD rs1196498041, REVEL 0.50, MetaLR 0.65
- G32S (p.Gly32Ser), TOPMed rs1196498041, gnomAD rs1196498041
- G32G (p.Gly32Gly), rs1428040722, gnomAD 17-72121487-C-T, CADD 15.00
- S33* (p.Ser33Ter), Ensembl rs2143237021, CADD 37.00
- S33A (p.Ser33Ala), Ensembl rs2143237011
- S33L (p.Ser33Leu), cosmic curated COSV55423, Ensembl rs2143237021, REVEL 0.52, MetaLR 0.76
- S33P (p.Ser33Pro), Ensembl rs2143237011
- S33T (p.Ser33Thr), Ensembl rs2143237011
- S33W (p.Ser33Trp), Ensembl rs2143237021
- S33S (p.Ser33Ser), rs761964967, gnomAD 17-72121490-G-T, CADD 13.20
Public SOX9 analysis runs
- SOX9 analysis run — SOX9 (2,691 variants) — completed 2026-08-19