CTNNB1 (Catenin beta-1) variants and mutations
CTNNB1 (also known as Catenin beta-1) is a human protein-coding gene encoding a catenin beta-1 protein. It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder. This analysis covers 3,448 CTNNB1 variants and mutations. Of these, 25% have computational variant effect predictions. Disease context includes severe intellectual disability-progressive spastic diplegia syndrome, pilomatrixoma, and hepatocellular carcinoma. Example CTNNB1 variants include M1?, M1V, and A2G.
Variant analysis overview
- Gene: CTNNB1
- Protein: Catenin beta-1
- UniProt accession: P35222
- Organism: Homo sapiens
- Variants analyzed: 3448
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 3,259 unspecified-consequence records; 33 missense variants; 2 stop-gained variants; 4 splice-region variants; 1 frameshift variants; 142 synonymous variants; 3 in-frame deletions; 4 substitution
- Prediction scores: 850 variants have prediction scores (25% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: severe intellectual disability-progressive spastic diplegia syndrome, pilomatrixoma, hepatocellular carcinoma, medulloblastoma, Familial exudative vitreoretinopathy, colorectal cancer, ovarian cancer, hepatoblastoma, prostate adenocarcinoma, listeriosis, cancer, hereditary disease.
Protein structure and variant hotspots
- Protein features: 20 post-translational modification sites.
- PTM context: 80 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 CTNNB1 variants
Examples include M1?, M1V, A2G, A2T, A2P, T3A, T3I, T3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV62697
- M1V (p.Met1Val), rs956534023, ClinGen CA74088417, ClinVar RCV001563600, MetaLR 0.10, MetaSVM -0.93, Uncertain significance, CTNNB1-related syndromic intellectual disability
- A2G (p.Ala2Gly), rs1310497035, ClinGen CA352227918, ClinVar RCV001900219, TOPMed rs1310497035, REVEL 0.12, CADD 23.10, Uncertain significance, not provided
- A2T (p.Ala2Thr), TOPMed rs1204596334, gnomAD rs1204596334
- A2P (p.Ala2Pro), gnomAD 3-41224072-G-C, REVEL 0.24, CADD 24.20
- T3A (p.Thr3Ala), NCI-TCGA Cosmic COSV6270, cosmic curated COSV62704, Variant assessed as somatic; moderate impact.
- T3I (p.Thr3Ile), cosmic curated COSV99051
- T3N (p.Thr3Asn), cosmic curated COSV62719, ExAC rs749331498, TOPMed rs749331498, gnomAD rs749331498
- T3S (p.Thr3Ser), cosmic curated COSV62700, ExAC rs749331498, TOPMed rs749331498, gnomAD rs749331498
- Q4H (p.Gln4His), cosmic curated COSV62701
- Q4P (p.Gln4Pro), Ensembl rs1575314399, REVEL 0.16, CADD 22.50
- Q4* (p.Gln4Ter), gnomAD 3-41224078-C-T, CADD 36.00
- A5G (p.Ala5Gly), rs1448779783, ClinGen CA352227952, ClinVar RCV002028107, TOPMed rs1448779783, REVEL 0.23, CADD 21.70, Uncertain significance, not provided
- A5V (p.Ala5Val), cosmic curated COSV62698, TOPMed rs1448779783, Uncertain significance
- A5A (p.Ala5Ala), rs2125616623, gnomAD 3-41224527-T-C, CADD 15.70
- D6A (p.Asp6Ala), cosmic curated COSV10084
- D6E (p.Asp6Glu), Ensembl rs2125616639
- D6G (p.Asp6Gly), cosmic curated COSV62688
- D6H (p.Asp6His), Ensembl rs2125616631
- D6I (p.Asp6Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D6N (p.Asp6Asn), Ensembl rs2125616631
- D6Y (p.Asp6Tyr), Ensembl rs2125616631, REVEL 0.45, CADD 25.20
- L7F (p.Leu7Phe), Ensembl rs2125616659, Uncertain significance, not provided
- L7S (p.Leu7Ser), Ensembl rs2125616655
- L7D (p.Leu7Asp), gnomAD 3-41224529-ATT-A, CADD 24.20
- L7L (p.Leu7Leu), rs1209058117, gnomAD 3-41224531-T-C, CADD 7.78
- M8I (p.Met8Ile), cosmic curated COSV99051, Ensembl rs2125616674, cosmic curated COSV62724, Uncertain significance, not provided
- M8T (p.Met8Thr), rs1559467552, ClinGen CA352227972, ClinVar RCV000681492, Likely benign, Intellectual disability
- E9* (p.Glu9Ter), cosmic curated COSV62691, Ensembl rs2125616693
- E9D (p.Glu9Asp), rs2078128295, TOPMed rs2078128295, ClinGen CA352227984, ClinVar RCV003033690, AlphaMissense 0.59, MetaLR 0.05, Uncertain significance, not provided
- E9K (p.Glu9Lys), cosmic curated COSV62718, Ensembl rs2125616693
- E9Q (p.Glu9Gln), Ensembl rs2125616693
- E9V (p.Glu9Val), Ensembl rs2125616705
- E9E (p.Glu9Glu), rs2078128295, gnomAD 3-41224539-G-A, AlphaMissense 0.59, MetaLR 0.05
- L10F (p.Leu10Phe), Ensembl rs2125616723
- L10V (p.Leu10Val), Ensembl rs2125616716
- L10L (p.Leu10Leu), gnomAD 3-41224540-T-C, CADD 8.93
- D11E (p.Asp11Glu), Ensembl rs2125616742, REVEL 0.14, CADD 14.30
- D11H (p.Asp11His), Ensembl rs2125616732
- D11N (p.Asp11Asn), cosmic curated COSV62731, Ensembl rs2125616732
- D11Y (p.Asp11Tyr), Ensembl rs2125616732
- M12I (p.Met12Ile), Ensembl rs2125616753, cosmic curated COSV62702
- M12L (p.Met12Leu), cosmic curated COSV10444, Ensembl rs2125616750
- M12T (p.Met12Thr), gnomAD 3-41224547-T-C, REVEL 0.20, CADD 20.80
- A13D (p.Ala13Asp), Ensembl rs2125616773
- A13G (p.Ala13Gly), Ensembl rs2125616773
- A13P (p.Ala13Pro), Ensembl rs121913394
- A13S (p.Ala13Ser), Ensembl rs121913394, REVEL 0.21, CADD 21.30
- A13T (p.Ala13Thr), cosmic curated COSV62704, Ensembl rs121913394
- A13V (p.Ala13Val), Ensembl rs2125616773, Uncertain significance, not provided
- A13A (p.Ala13Ala), rs2125616783, gnomAD 3-41224551-C-T, CADD 12.80
- M14I (p.Met14Ile), Ensembl rs2125616790
- M14T (p.Met14Thr), rs2470773619, ClinGen CA352228017, ClinVar RCV003024347, Uncertain significance, not provided
- M14V (p.Met14Val), rs752642845, ClinGen CA2330855, cosmic curated COSV62723, ClinVar RCV000513017, REVEL 0.18, CADD 19.10, Uncertain significance, not provided
- E15* (p.Glu15Ter), Ensembl rs1575315288, Uncertain significance
- E15D (p.Glu15Asp), rs587778221, ClinGen CA158228, ClinVar RCV000120620, Ensembl rs587778221, AlphaMissense 0.20, MetaLR 0.06, not provided, not specified
- E15G (p.Glu15Gly), TOPMed rs2078128617, REVEL 0.21, CADD 23.10
- E15K (p.Glu15Lys), rs1575315288, ClinGen CA352228024, cosmic curated COSV62704, ClinVar RCV000786916, AlphaMissense 0.92, MetaLR 0.08, Uncertain significance, Severe intellectual disability-progressive spastic diplegia syndrome
- E15Q (p.Glu15Gln), Ensembl rs1575315288, Uncertain significance
- E15V (p.Glu15Val), TOPMed rs2078128617
- P16A (p.Pro16Ala), gnomAD rs1290293308
- P16L (p.Pro16Leu), cosmic curated COSV62727, cosmic curated COSV62719, gnomAD rs1453594408
- P16R (p.Pro16Arg), gnomAD rs1453594408, REVEL 0.17, CADD 22.40
- P16S (p.Pro16Ser), cosmic curated COSV62695, gnomAD rs1290293308
- P16T (p.Pro16Thr), cosmic curated COSV10084, gnomAD rs1290293308, REVEL 0.14, CADD 21.60
- P16P (p.Pro16Pro), gnomAD 3-41224560-A-G, CADD 11.40
- D17E (p.Asp17Glu), Ensembl rs2125616866
- D17G (p.Asp17Gly), Ensembl rs2125616858
- D17H (p.Asp17His), cosmic curated COSV62729, Ensembl rs2125616849
- D17N (p.Asp17Asn), Ensembl rs2125616849
- D17V (p.Asp17Val), Ensembl rs2125616858
- D17Y (p.Asp17Tyr), cosmic curated COSV62703
- R18* (p.Arg18Ter), TOPMed rs1213896677, gnomAD rs1213896677
- R18K (p.Arg18Lys), cosmic curated COSV10084
- R18S (p.Arg18Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R18G (p.Arg18Gly), gnomAD 3-41224564-A-G, REVEL 0.34, CADD 22.20
- R18R (p.Arg18Arg), rs1213896677, gnomAD 3-41224564-A-C, CADD 13.10
- K19* (p.Lys19Ter), Ensembl rs2125616881
- K19I (p.Lys19Ile), Ensembl rs2125616888
- K19N (p.Lys19Asn), Ensembl rs2125616897
- K19R (p.Lys19Arg), Ensembl rs2125616888
- K19T (p.Lys19Thr), Ensembl rs2125616888
- A20E (p.Ala20Glu), ExAC rs757325337, gnomAD rs757325337, Uncertain significance
- A20G (p.Ala20Gly), ExAC rs757325337, gnomAD rs757325337, Uncertain significance
- A20P (p.Ala20Pro), Ensembl rs2125616908
- A20R (p.Ala20Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A20T (p.Ala20Thr), Ensembl rs2125616908
- A20V (p.Ala20Val), rs757325337, ClinGen CA2330856, cosmic curated COSV62708, ClinVar RCV002030176, REVEL 0.09, CADD 21.80, Uncertain significance, CTNNB1-related disorder; not provided
- A20A (p.Ala20Ala), rs1044865901, gnomAD 3-41224572-G-A, CADD 1.08
- A21D (p.Ala21Asp), cosmic curated COSV62724, Ensembl rs2125616940
- A21G (p.Ala21Gly), Ensembl rs2125616940
- A21P (p.Ala21Pro), Ensembl rs121913395, Uncertain significance
- A21S (p.Ala21Ser), Ensembl rs121913395, Uncertain significance
- A21T (p.Ala21Thr), rs121913395, ClinGen CA16602677, NCI-TCGA Cosmic COSV6269, cosmic curated COSV62699, AlphaMissense 0.22, MetaLR 0.09, Uncertain significance, not provided
- A21V (p.Ala21Val), cosmic curated COSV62713, Ensembl rs2125616940
- V22A (p.Val22Ala), cosmic curated COSV62698, ExAC rs77064436, gnomAD rs77064436
- V22D (p.Val22Asp), NCI-TCGA Cosmic COSV6269, ExAC rs77064436, gnomAD rs77064436, Variant assessed as somatic; moderate impact.
- V22G (p.Val22Gly), cosmic curated COSV62692, ExAC rs77064436, gnomAD rs77064436
- V22I (p.Val22Ile), cosmic curated COSV62693, Ensembl rs2125616960
- V22L (p.Val22Leu), Ensembl rs2125616960
- S23C (p.Ser23Cys), TOPMed rs1413975856, gnomAD rs1413975856, Uncertain significance, in hepatocellular carcinoma
- S23G (p.Ser23Gly), rs1413975856, ClinGen CA352228073, cosmic curated COSV62721, ClinVar RCV003437772, AlphaMissense 0.62, MetaLR 0.09, Uncertain significance, not provided
- S23N (p.Ser23Asn), cosmic curated COSV62688, Ensembl rs2125616998
- S23R (p.Ser23Arg), rs1413975856, cosmic curated COSV62697, UniProt VAR 017612, TOPMed rs1413975856, REVEL 0.19, AlphaMissense 0.62, Uncertain significance, in hepatocellular carcinoma
- H24D (p.His24Asp), Ensembl rs2125617012
- H24L (p.His24Leu), rs2125617021, ClinGen CA352228449, ClinVar RCV003048931, Ensembl rs2125617021, AlphaMissense 0.62, MetaLR 0.09, Uncertain significance, not provided
- H24N (p.His24Asn), Ensembl rs2125617012
- H24P (p.His24Pro), Ensembl rs2125617021, Uncertain significance
- H24Q (p.His24Gln), cosmic curated COSV62697, Ensembl rs2125617029
- H24R (p.His24Arg), cosmic curated COSV62714, Ensembl rs2125617021, Uncertain significance
- H24Y (p.His24Tyr), cosmic curated COSV62712, Ensembl rs2125617012
- H24H (p.His24His), rs2125617029, gnomAD 3-41224584-C-T, CADD 10.60
- W25* (p.Trp25Ter), cosmic curated COSV62703, Ensembl rs2125617039
- W25C (p.Trp25Cys), Ensembl rs2125617047
- W25L (p.Trp25Leu), cosmic curated COSV62689
- W25R (p.Trp25Arg), cosmic curated COSV62695
- W25S (p.Trp25Ser), Ensembl rs2125617039
- Q26H (p.Gln26His), cosmic curated COSV10606, TOPMed rs1159520578, gnomAD rs1159520578, REVEL 0.16, CADD 21.90
- Q26L (p.Gln26Leu), Ensembl rs2125617063, Uncertain significance
- Q26R (p.Gln26Arg), rs2125617063, cosmic curated COSV62708, ClinGen CA352228465, cosmic curated COSV62694, AlphaMissense 0.97, MetaLR 0.17, Uncertain significance, not provided
- Q27* (p.Gln27Ter), cosmic curated COSV62688, Ensembl rs2125617076
- Q27E (p.Gln27Glu), Ensembl rs2125617076
- Q27H (p.Gln27His), cosmic curated COSV62688, 1000Genomes rs369714835, ESP rs369714835, ExAC rs369714835, Likely benign
- Q27K (p.Gln27Lys), Ensembl rs2125617076
- Q27L (p.Gln27Leu), Ensembl rs2125617087
- Q27Q (p.Gln27Gln), rs369714835, gnomAD 3-41224593-A-G, CADD 7.42
- Q28* (p.Gln28Ter), cosmic curated COSV62728, Ensembl rs2125617101
- Q28E (p.Gln28Glu), cosmic curated COSV62697, Ensembl rs2125617101
- Q28H (p.Gln28His), rs1258632801, gnomAD rs1258632801, ClinGen CA352228484, ClinVar RCV002299570, REVEL 0.18, CADD 16.60, Uncertain significance, not provided
- Q28L (p.Gln28Leu), Ensembl rs2125617109
- Q28R (p.Gln28Arg), cosmic curated COSV62697, Ensembl rs2125617109, REVEL 0.20, CADD 23.80
- S29A (p.Ser29Ala), cosmic curated COSV62691, Ensembl rs2125617130
- S29C (p.Ser29Cys), rs2078130210, ClinGen CA352228488, ClinVar RCV003433528, TOPMed rs2078130210, AlphaMissense 1.00, MetaLR 0.11, Uncertain significance, not provided
- S29F (p.Ser29Phe), cosmic curated COSV62688, TOPMed rs2078130210, Uncertain significance
- S29P (p.Ser29Pro), cosmic curated COSV62710
- S29T (p.Ser29Thr), Ensembl rs2125617130
- S29Y (p.Ser29Tyr), cosmic curated COSV62712
- Y30* (p.Tyr30Ter), NCI-TCGA TCGA novel, cosmic curated COSV62692, cosmic curated COSV62712, Ensembl rs2125617172, Variant assessed as somatic; high impact.
- Y30C (p.Tyr30Cys), cosmic curated COSV62716, Ensembl rs2125617162
- Y30D (p.Tyr30Asp), Ensembl rs2125617157
- Y30F (p.Tyr30Phe), Ensembl rs2125617162
- Y30N (p.Tyr30Asn), Ensembl rs2125617157
- Y30S (p.Tyr30Ser), cosmic curated COSV62698, Ensembl rs2125617162
- L31M (p.Leu31Met), cosmic curated COSV62692, ExAC rs758657130, gnomAD rs758657130
- L31P (p.Leu31Pro), cosmic curated COSV62704
- L31Q (p.Leu31Gln), cosmic curated COSV62689
- L31V (p.Leu31Val), ExAC rs758657130, gnomAD rs758657130
- L31W (p.Leu31Trp), cosmic curated COSV62705
- L31L (p.Leu31Leu), rs758657130, gnomAD 3-41224603-C-T, CADD 10.60
- D32A (p.Asp32Ala), rs121913396, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62688, AlphaMissense 1.00, MetaLR 0.32, Tier I - Strong, Embryonal rhabdomyosarcoma; Medulloblastoma WNT activated
- D32C (p.Asp32Cys), cosmic curated COSV62698
- D32E (p.Asp32Glu), cosmic curated COSV62690, Ensembl rs2125617206, cosmic curated COSV62688
- D32G (p.Asp32Gly), rs121913396, ClinGen CA127265, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62688, AlphaMissense 1.00, MetaLR 0.32, Pathogenic/Likely pathogenic, not provided; Pilomatrixoma
- D32H (p.Asp32His), rs28931588, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.34, Tier I - Strong, Adamantinous craniopharyngioma; Adrenal cortex carcinoma; Medulloblastoma WNT ac
- D32N (p.Asp32Asn), rs28931588, ClinGen CA16602681, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62687, AlphaMissense 1.00, MetaLR 0.34, Pathogenic, Juvenile nasopharyngeal angiofibroma
- D32V (p.Asp32Val), rs121913396, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.32, Likely oncogenic, Neoplasm
- D32Y (p.Asp32Tyr), rs28931588, ClinGen CA127271, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.34, Pathogenic; other, Pilomatrixoma; Hepatoblastoma; Medulloblastoma
- D32D (p.Asp32Asp), gnomAD 3-41224608-C-T, CADD 9.57
- S33A (p.Ser33Ala), rs1057519886, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62689, AlphaMissense 0.91, MetaLR 0.32, Tier I - Strong, Medulloblastoma WNT activated
- S33C (p.Ser33Cys), rs121913400, ClinGen CA16602684, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62687, AlphaMissense 1.00, MetaLR 0.34, other, Medulloblastoma
- S33F (p.Ser33Phe), rs121913400, ClinGen CA127275, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.34, Pathogenic; other, Malignant tumor of urinary bladder; Pilomatrixoma; Medulloblastoma
- S33L (p.Ser33Leu), cosmic curated COSV62703, UniProt VAR 017618, Uncertain significance, in hepatocellular carcinoma
- S33N (p.Ser33Asn), cosmic curated COSV62688
- S33P (p.Ser33Pro), rs1057519886, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62688, AlphaMissense 0.91, MetaLR 0.32, Likely pathogenic, in colorectal cancer and PTR
- S33T (p.Ser33Thr), rs1057519886, NCI-TCGA Cosmic COSV6268, NCI-TCGA Cosmic COSV6270, AlphaMissense 0.91, MetaLR 0.32, Likely pathogenic, in colorectal cancer and PTR
- S33Y (p.Ser33Tyr), rs121913400, ClinGen CA127263, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.34, Pathogenic, Pilomatrixoma; Carcinoma of colon
- G34* (p.Gly34Ter), cosmic curated COSV62721, Ensembl rs121913399, Pathogenic, in hepatoblastoma
- G34A (p.Gly34Ala), cosmic curated COSV62692, ExAC rs28931589, gnomAD rs28931589, Pathogenic, in hepatoblastoma
- G34D (p.Gly34Asp), cosmic curated COSV62708
- G34E (p.Gly34Glu), rs28931589, ClinGen CA127277, NCI-TCGA Cosmic COSV6268, AlphaMissense 1.00, MetaLR 0.34, Pathogenic; other, Pilomatrixoma; Medulloblastoma
- G34I (p.Gly34Ile), cosmic curated COSV62689, Ensembl rs2125617258
- G34L (p.Gly34Leu), cosmic curated COSV62715
- G34R (p.Gly34Arg), rs121913399, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62687, AlphaMissense 1.00, MetaLR 0.34, Tier I - Strong, Adrenal cortex carcinoma
- G34V (p.Gly34Val), rs28931589, ClinGen CA127273, NCI-TCGA Cosmic COSV6268, cosmic curated COSV62687, AlphaMissense 1.00, MetaLR 0.34, Likely pathogenic, Colorectal cancer
- I35F (p.Ile35Phe), Ensembl rs2125617286
- I35K (p.Ile35Lys), cosmic curated COSV62695, Ensembl rs2125617313
- I35L (p.Ile35Leu), Ensembl rs2125617286
- I35M (p.Ile35Met), cosmic curated COSV62694, Ensembl rs2125617323
- I35N (p.Ile35Asn), cosmic curated COSV62693, Ensembl rs2125617301
- I35S (p.Ile35Ser), NCI-TCGA Cosmic COSV6268, cosmic curated COSV62687, NCI-TCGA Cosmic COSV6269, Uncertain significance, in hepatocellular carcinoma
Public CTNNB1 analysis runs
- CTNNB1 analysis run — CTNNB1 (3,448 variants) — completed 2026-08-18