CDKN1A (P38936) variants and mutations
CDKN1A (also known as P38936) is a human protein-coding gene encoding a cyclin-dependent kinase inhibitor 1 protein. It inhibits cyclin-CDK complexes after DNA damage or other stress and can impose cell-cycle arrest downstream of p53. Altered p21 regulation affects senescence, DNA-damage responses, and cancer-cell sensitivity to therapy. This analysis covers 768 CDKN1A variants and mutations. Of these, 24% have computational variant effect predictions. Disease context includes neurodegenerative disease, response to statin, and ocular hypotension. Example CDKN1A variants include M1?, S2*, and S2A.
Variant analysis overview
- Gene: CDKN1A
- Protein: P38936
- UniProt accession: P38936
- Organism: Homo sapiens
- Variants analyzed: 768
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 632 unspecified-consequence records; 2 stop lost; 43 synonymous variants; 73 missense variants; 2 stop-gained variants; 9 frameshift variants; 3 splice-region variants; 1 stop retained variant; 2 in-frame deletions; 1 substitution
- Prediction scores: 182 variants have prediction scores (24% of the analyzed set).
Clinical, disease, and population context
- Disease context: 13 disease associations are represented. Top associations: neurodegenerative disease, response to statin, ocular hypotension, infection, ovarian serous cystadenocarcinoma, thyroid cancer, nonmedullary, 1, nonpapillary renal cell carcinoma, cervical cancer, hereditary breast carcinoma, papillary renal cell carcinoma, esophageal cancer, Hereditary breast cancer.
Protein structure and variant hotspots
- Protein features: 7 post-translational modification sites.
- PTM context: 27 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CDKN1A variants
Examples include M1?, S2*, S2A, S2P, S2T, S2S, E3D, E3G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV55188, NCI-TCGA Cosmic COSV5518, cosmic curated COSV55187, Variant assessed as somatic; high impact.
- S2* (p.Ser2Ter), cosmic curated COSV55190
- S2A (p.Ser2Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S2P (p.Ser2Pro), ESP rs371219528
- S2T (p.Ser2Thr), ESP rs371219528
- S2S (p.Ser2Ser), gnomAD 22-46248276-G-C, CADD 0.43
- E3D (p.Glu3Asp), Ensembl rs1582580745
- E3G (p.Glu3Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E3K (p.Glu3Lys), Ensembl rs1762105141
- E3* (p.Glu3Ter), gnomAD 22-46248245-C-CA, CADD 19.80
- E3E (p.Glu3Glu), gnomAD 22-46248267-C-T, CADD 1.08
- E3A (p.Glu3Ala), rs1433136546, gnomAD 22-46248268-T-G, REVEL 0.11, MetaLR 0.12
- P4A (p.Pro4Ala), Ensembl rs2150312696
- P4L (p.Pro4Leu), rs4986866, ClinGen CA3780300, cosmic curated COSV10879, ClinVar RCV000952903, AlphaMissense 0.06, MetaLR 0.17, Benign, not provided
- P4Q (p.Pro4Gln), 1000Genomes rs4986866, ESP rs4986866, ExAC rs4986866, TOPMed rs4986866, Benign
- P4R (p.Pro4Arg), 1000Genomes rs4986866, ESP rs4986866, ExAC rs4986866, TOPMed rs4986866, Benign
- P4S (p.Pro4Ser), NCI-TCGA Cosmic COSV5519, cosmic curated COSV55191, Ensembl rs2150312696, Variant assessed as somatic; moderate impact.
- A5G (p.Ala5Gly), Ensembl rs2150312732
- A5P (p.Ala5Pro), Ensembl rs2150312726
- A5T (p.Ala5Thr), Ensembl rs2150312726
- A5V (p.Ala5Val), cosmic curated COSV99781, Ensembl rs2150312732
- A5A (p.Ala5Ala), gnomAD 22-46248279-C-A, CADD 0.27
- A5E (p.Ala5Glu), gnomAD 22-46248280-G-T, REVEL 0.04, MetaLR 0.04
- A5S (p.Ala5Ser), gnomAD 22-46248281-C-A, REVEL 0.04, MetaLR 0.08
- G6A (p.Gly6Ala), ExAC rs764986724, gnomAD rs764986724
- G6R (p.Gly6Arg), TOPMed rs1378686749, gnomAD rs1378686749
- G6V (p.Gly6Val), ExAC rs764986724, gnomAD rs764986724
- D7E (p.Asp7Glu), TOPMed rs1312466117, gnomAD rs1312466117
- D7G (p.Asp7Gly), Ensembl rs2150312749
- D7N (p.Asp7Asn), NCI-TCGA Cosmic COSV9978, cosmic curated COSV99781, Ensembl rs2150312746, Variant assessed as somatic; moderate impact.
- V8A (p.Val8Ala), Ensembl rs2150312759
- V8I (p.Val8Ile), Ensembl rs2150312755
- V8M (p.Val8Met), gnomAD 22-46248251-C-T, REVEL 0.00, MetaLR 0.04
- V8V (p.Val8Val), rs1936523367, gnomAD 22-46248270-T-C, CADD 0.36
- V8E (p.Val8Glu), gnomAD 22-46248271-A-T, REVEL 0.03, MetaLR 0.03
- R9C (p.Arg9Cys), ExAC rs752557277, TOPMed rs752557277, gnomAD rs752557277
- R9G (p.Arg9Gly), ExAC rs752557277, TOPMed rs752557277, gnomAD rs752557277
- R9H (p.Arg9His), rs143419412, NCI-TCGA Cosmic COSV5518, 1000Genomes rs143419412, ESP rs143419412, AlphaMissense 0.09, MetaLR 0.19, Variant assessed as somatic; moderate impact.
- R9P (p.Arg9Pro), NCI-TCGA Cosmic COSV5518, cosmic curated COSV55187, 1000Genomes rs143419412, ESP rs143419412, Variant assessed as somatic; moderate impact.
- R8del (p.Arg8del), rs1377495993, gnomAD 22-46248261-ACGG-, CADD 5.11
- Q10* (p.Gln10Ter), NCI-TCGA Cosmic COSV5518, cosmic curated COSV55186, Variant assessed as somatic; high impact.
- N11T (p.Asn11Thr), Ensembl rs1582580943
- P12H (p.Pro12His), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P12L (p.Pro12Leu), cosmic curated COSV10960
- P12S (p.Pro12Ser), gnomAD 22-46248260-G-A, REVEL 0.05, MetaLR 0.07
- C13* (p.Cys13Ter), cosmic curated COSV55191, ExAC rs756319938, TOPMed rs756319938, gnomAD rs756319938
- C13G (p.Cys13Gly), 1000Genomes rs199896504, ExAC rs199896504, TOPMed rs199896504, gnomAD rs199896504
- C13R (p.Cys13Arg), 1000Genomes rs199896504, ExAC rs199896504, TOPMed rs199896504, gnomAD rs199896504
- C13S (p.Cys13Ser), 1000Genomes rs199896504, ExAC rs199896504, TOPMed rs199896504, gnomAD rs199896504
- C13W (p.Cys13Trp), ExAC rs756319938, TOPMed rs756319938, gnomAD rs756319938
- C13Y (p.Cys13Tyr), gnomAD 22-46248241-C-T, REVEL 0.68, MetaLR 0.46
- C13C (p.Cys13Cys), rs775238485, gnomAD 22-46248264-G-A, CADD 2.54
- G14A (p.Gly14Ala), Ensembl rs2150312802
- G14C (p.Gly14Cys), 1000Genomes rs576307617, ExAC rs576307617, TOPMed rs576307617, gnomAD rs576307617
- G14D (p.Gly14Asp), cosmic curated COSV55191, Ensembl rs2150312802
- G14R (p.Gly14Arg), 1000Genomes rs576307617, ExAC rs576307617, TOPMed rs576307617, gnomAD rs576307617
- G14S (p.Gly14Ser), rs576307617, cosmic curated COSV10584, 1000Genomes rs576307617, ExAC rs576307617, AlphaMissense 0.13, MetaLR 0.24, Likely benign, not specified
- G14V (p.Gly14Val), Ensembl rs2150312802
- G14E (p.Gly14Glu), gnomAD 22-46248252-TC-T, CADD 24.70
- G14G (p.Gly14Gly), gnomAD 22-46248252-T-G, CADD 2.01
- S15G (p.Ser15Gly), cosmic curated COSV55190, TOPMed rs1213732148, gnomAD rs1213732148
- S15N (p.Ser15Asn), gnomAD rs866551255
- S15R (p.Ser15Arg), NCI-TCGA Cosmic COSV5518, Variant assessed as somatic; high impact.
- S15T (p.Ser15Thr), gnomAD rs866551255
- K16* (p.Lys16Ter), Ensembl rs2150312829
- K16G (p.Lys16Gly), NCI-TCGA Cosmic COSV5518, Variant assessed as somatic; high impact.
- K16N (p.Lys16Asn), Ensembl rs1762108413
- K16R (p.Lys16Arg), gnomAD rs1412876146
- K16K (p.Lys16Lys), rs780335206, gnomAD 22-46248195-C-T, CADD 7.53
- K16T (p.Lys16Thr), rs1048980837, gnomAD 22-46248196-T-G, REVEL 0.10, MetaLR 0.16
- A17P (p.Ala17Pro), Ensembl rs2150312837, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A17S (p.Ala17Ser), Ensembl rs2150312837
- A17T (p.Ala17Thr), Ensembl rs2150312837
- A17G (p.Ala17Gly), gnomAD 22-46248220-G-C, REVEL 0.23, MetaLR 0.23
- C18* (p.Cys18Ter), Ensembl rs1762108775
- C18S (p.Cys18Ser), gnomAD rs1424157871
- C18W (p.Cys18Trp), Ensembl rs1762108775
- C18Y (p.Cys18Tyr), gnomAD rs1424157871
- C18G (p.Cys18Gly), gnomAD 22-46248233-A-C, REVEL 0.75, MetaLR 0.44
- R19C (p.Arg19Cys), ExAC rs769229553, TOPMed rs769229553, gnomAD rs769229553
- R19H (p.Arg19His), cosmic curated COSV55187, ExAC rs779250316, TOPMed rs779250316, gnomAD rs779250316
- R19L (p.Arg19Leu), ExAC rs779250316, TOPMed rs779250316, gnomAD rs779250316
- R19P (p.Arg19Pro), ExAC rs779250316, TOPMed rs779250316, gnomAD rs779250316
- R20C (p.Arg20Cys), ExAC rs748554042, TOPMed rs748554042, gnomAD rs748554042
- R20H (p.Arg20His), rs375050346, ClinGen CA3780315, cosmic curated COSV55189, ClinVar RCV004167878, AlphaMissense 0.25, MetaLR 0.25, Uncertain significance, not specified
- R20L (p.Arg20Leu), ESP rs375050346, ExAC rs375050346, TOPMed rs375050346, gnomAD rs375050346, Uncertain significance
- R20P (p.Arg20Pro), ESP rs375050346, ExAC rs375050346, TOPMed rs375050346, gnomAD rs375050346, Uncertain significance
- L21F (p.Leu21Phe), cosmic curated COSV55191, Ensembl rs2150312878
- L21H (p.Leu21His), Ensembl rs2150312884
- L21I (p.Leu21Ile), Ensembl rs2150312878
- L21P (p.Leu21Pro), Ensembl rs2150312884
- L21V (p.Leu21Val), Ensembl rs2150312878
- L21R (p.Leu21Arg), rs770424793, gnomAD 22-46248235-A-C, REVEL 0.60, MetaLR 0.33
- L21L (p.Leu21Leu), gnomAD 22-46248255-C-T, CADD 7.01
- L21M (p.Leu21Met), gnomAD 22-46248257-G-T, REVEL 0.04, MetaLR 0.10
- F22I (p.Phe22Ile), Ensembl rs2150312894
- F22L (p.Phe22Leu), ExAC rs746664004, TOPMed rs746664004, gnomAD rs746664004, NCI-TCGA Cosmic COSV5518, Variant assessed as somatic; high impact.
- F22S (p.Phe22Ser), TOPMed rs1253386083
- G23C (p.Gly23Cys), cosmic curated COSV10807, ExAC rs770464093, TOPMed rs770464093, gnomAD rs770464093
- G23D (p.Gly23Asp), ESP rs368128681, ExAC rs368128681, TOPMed rs368128681, gnomAD rs368128681
- G23R (p.Gly23Arg), ExAC rs770464093, TOPMed rs770464093, gnomAD rs770464093
- G23S (p.Gly23Ser), ExAC rs770464093, TOPMed rs770464093, gnomAD rs770464093
- G23V (p.Gly23Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P24A (p.Pro24Ala), gnomAD rs1276639827
- P24L (p.Pro24Leu), Ensembl rs2150312928
- P24Q (p.Pro24Gln), cosmic curated COSV10960, Ensembl rs2150312928
- P24S (p.Pro24Ser), cosmic curated COSV55189, gnomAD rs1276639827
- P24T (p.Pro24Thr), gnomAD rs1276639827
- P24P (p.Pro24Pro), rs778898630, gnomAD 22-46248189-G-A, CADD 0.83
- V25A (p.Val25Ala), ExAC rs765248879, TOPMed rs765248879, gnomAD rs765248879, Uncertain significance
- V25E (p.Val25Glu), ExAC rs765248879, TOPMed rs765248879, gnomAD rs765248879, Uncertain significance
- V25G (p.Val25Gly), rs765248879, ClinGen CA3780321, cosmic curated COSV10584, ClinVar RCV004141616, AlphaMissense 0.77, MetaLR 0.58, Uncertain significance, not specified
- V25L (p.Val25Leu), ESP rs151314631, ExAC rs151314631, TOPMed rs151314631, gnomAD rs151314631
- V25M (p.Val25Met), ESP rs151314631, ExAC rs151314631, TOPMed rs151314631, gnomAD rs151314631
- V25S (p.Val25Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V25V (p.Val25Val), gnomAD 22-46247221-G-T, CADD 8.50, SIFT 0.24
- V25D (p.Val25Asp), gnomAD 22-46248172-A-T, REVEL 0.28, MetaLR 0.28
- D26E (p.Asp26Glu), Ensembl rs2150312965
- D26G (p.Asp26Gly), Ensembl rs2150312957
- D26H (p.Asp26His), Ensembl rs2150312952
- D26V (p.Asp26Val), Ensembl rs2150312957
- D26Y (p.Asp26Tyr), Ensembl rs2150312952
- S27C (p.Ser27Cys), ExAC rs775222810, TOPMed rs775222810, gnomAD rs775222810
- S27G (p.Ser27Gly), ExAC rs775222810, TOPMed rs775222810, gnomAD rs775222810
- S27I (p.Ser27Ile), gnomAD rs1277785976
- S27K (p.Ser27Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S27N (p.Ser27Asn), cosmic curated COSV10730, gnomAD rs1277785976
- S27R (p.Ser27Arg), ExAC rs762818650, TOPMed rs762818650, gnomAD rs762818650, Likely benign
- S27T (p.Ser27Thr), cosmic curated COSV55187, gnomAD rs1277785976
- E28* (p.Glu28Ter), cosmic curated COSV55189, ExAC rs763967941, TOPMed rs763967941, gnomAD rs763967941
- E28D (p.Glu28Asp), 1000Genomes rs537336408, ExAC rs537336408, gnomAD rs537336408
- E28G (p.Glu28Gly), Ensembl rs2150312991
- E28K (p.Glu28Lys), cosmic curated COSV55191, ExAC rs763967941, TOPMed rs763967941, gnomAD rs763967941, Uncertain significance, not specified
- E28Q (p.Glu28Gln), ExAC rs763967941, TOPMed rs763967941, gnomAD rs763967941
- E28V (p.Glu28Val), Ensembl rs2150312991
- Q29* (p.Gln29Ter), cosmic curated COSV55191, cosmic curated COSV55189, TOPMed rs1404633931, gnomAD rs1404633931
- Q29E (p.Gln29Glu), TOPMed rs1404633931, gnomAD rs1404633931
- Q29K (p.Gln29Lys), TOPMed rs1404633931, gnomAD rs1404633931
- Q29P (p.Gln29Pro), ExAC rs756383281, TOPMed rs756383281, gnomAD rs756383281, Uncertain significance, not specified
- Q29R (p.Gln29Arg), ExAC rs756383281, TOPMed rs756383281, gnomAD rs756383281
- Q29V (p.Gln29Val), gnomAD 22-46248180-CTG-C, CADD 24.90
- L30M (p.Leu30Met), Ensembl rs2150313012
- L30P (p.Leu30Pro), Ensembl rs2150313019
- L30Q (p.Leu30Gln), Ensembl rs2150313019
- L30V (p.Leu30Val), Ensembl rs2150313012
- S31R (p.Ser31Arg), rs1801270, ClinGen CA127261, cosmic curated COSV55187, ClinVar RCV000019125, AlphaMissense 0.08, MetaLR 0.08, Benign, CIP1/WAF1 TUMOR-ASSOCIATED POLYMORPHISM 1
- S31S (p.Ser31Ser), rs540181007, gnomAD 22-46247149-C-T, CADD 0.11, SIFT 0.19
- S31L (p.Ser31Leu), rs758111260, gnomAD 22-46247150-G-A, REVEL 0.46, MetaLR 0.31
- S31P (p.Ser31Pro), rs1309197084, gnomAD 22-46247151-A-G, REVEL 0.32, MetaLR 0.31
- S31N (p.Ser31Asn), gnomAD 22-46247207-C-T, REVEL 0.18, MetaLR 0.20
- R32C (p.Arg32Cys), cosmic curated COSV55192, ESP rs373450720, ExAC rs373450720, TOPMed rs373450720
- R32G (p.Arg32Gly), ESP rs373450720, ExAC rs373450720, TOPMed rs373450720, gnomAD rs373450720
- R32H (p.Arg32His), NCI-TCGA Cosmic COSV5519, cosmic curated COSV55191, TOPMed rs1477458254, gnomAD rs1477458254, Uncertain significance, not specified
- R32L (p.Arg32Leu), TOPMed rs1477458254, gnomAD rs1477458254
- R32P (p.Arg32Pro), TOPMed rs1477458254, gnomAD rs1477458254
- D33E (p.Asp33Glu), cosmic curated COSV10584, TOPMed rs765503766, gnomAD rs765503766
- D33G (p.Asp33Gly), Ensembl rs2150313062
- D33H (p.Asp33His), ESP rs376481017, ExAC rs376481017, TOPMed rs376481017, gnomAD rs376481017, Uncertain significance, not specified
- D33N (p.Asp33Asn), rs376481017, NCI-TCGA Cosmic COSV5518, cosmic curated COSV55188, ESP rs376481017, AlphaMissense 0.73, MetaLR 0.68, Uncertain significance
- D33V (p.Asp33Val), Ensembl rs2150313062
- C34* (p.Cys34Ter), cosmic curated COSV10504, Ensembl rs2150313076
- C34S (p.Cys34Ser), TOPMed rs1412232353, gnomAD rs1412232353
- C34W (p.Cys34Trp), Ensembl rs2150313076
- C34Y (p.Cys34Tyr), TOPMed rs1412232353, gnomAD rs1412232353
- D35E (p.Asp35Glu), 1000Genomes rs201800542, ExAC rs201800542, TOPMed rs201800542, gnomAD rs201800542
- D35G (p.Asp35Gly), Ensembl rs2150313095
- D35H (p.Asp35His), Ensembl rs2150313082
- D35V (p.Asp35Val), Ensembl rs2150313095
- D35Y (p.Asp35Tyr), Ensembl rs2150313082
- A36E (p.Ala36Glu), ExAC rs746709171, TOPMed rs746709171, gnomAD rs746709171
- A36G (p.Ala36Gly), ExAC rs746709171, TOPMed rs746709171, gnomAD rs746709171
- A36P (p.Ala36Pro), Ensembl rs2150313106
- A36V (p.Ala36Val), rs746709171, NCI-TCGA Cosmic COSV9978, cosmic curated COSV99781, ExAC rs746709171, AlphaMissense 0.18, MetaLR 0.42, Variant assessed as somatic; moderate impact.
- L37I (p.Leu37Ile), Ensembl rs2150313117
- L37P (p.Leu37Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L37V (p.Leu37Val), Ensembl rs2150313117, Uncertain significance, not specified
- L37S (p.Leu37Ser), rs759612189, gnomAD 22-46247217-G-GGA, CADD 27.90
- M38I (p.Met38Ile), Ensembl rs2150313128
- M38N (p.Met38Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M38R (p.Met38Arg), Ensembl rs2150313125
Public CDKN1A analysis runs
- CDKN1A analysis run — CDKN1A (768 variants) — completed 2026-08-19