CCND1 (G1/S-specific cyclin-D1) variants and mutations
CCND1 (also known as G1/S-specific cyclin-D1) is a human protein-coding gene encoding a g1/S-specific cyclin-D1 protein. It partners with CDK4 and CDK6 to phosphorylate RB-family proteins and promote progression through the G1 phase of the cell cycle. Amplification, translocation, or overexpression drives many cancers, including mantle-cell lymphoma and subsets of breast cancer. This analysis covers 1,421 CCND1 variants and mutations. Of these, 55% have computational variant effect predictions. Disease context includes breast cancer, breast carcinoma, and plasma cell myeloma. Example CCND1 variants include E2A, E2D, and E2G.
Variant analysis overview
- Gene: CCND1
- Protein: G1/S-specific cyclin-D1
- UniProt accession: P24385
- Organism: Homo sapiens
- Variants analyzed: 1421
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,268 unspecified-consequence records; 45 missense variants; 92 synonymous variants; 5 stop-gained variants; 5 in-frame deletions; 1 frameshift variants; 1 splice-region variants; 4 substitution
- Prediction scores: 786 variants have prediction scores (55% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: breast cancer, breast carcinoma, plasma cell myeloma, neurodegenerative disease, breast neoplasm, prostate carcinoma, AL amyloidosis, type 2 diabetes mellitus, neoplasm, diabetes mellitus, endometrial cancer, von Hippel-Lindau disease.
Protein structure and variant hotspots
- Protein features: 1 domains; 1 post-translational modification sites.
- Structural context: 633 variants have structural context.
- PTM context: 5 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, MaveDB, LitVar.
Notable CCND1 variants
Examples include E2A, E2D, E2G, E2K, E2Q, H3D, H3L, H3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2A (p.Glu2Ala), Ensembl rs1855696258, REVEL 0.10, CADD 21.80
- E2D (p.Glu2Asp), Ensembl rs2120079566
- E2G (p.Glu2Gly), Ensembl rs1855696258, MetaLR 0.02, MetaSVM -1.06
- E2K (p.Glu2Lys), 1000Genomes rs572037183, ExAC rs572037183, TOPMed rs572037183, gnomAD rs572037183, REVEL 0.11, CADD 23.80
- E2Q (p.Glu2Gln), 1000Genomes rs572037183, ExAC rs572037183, TOPMed rs572037183, gnomAD rs572037183, REVEL 0.10, CADD 23.30
- H3D (p.His3Asp), Ensembl rs2120079579
- H3L (p.His3Leu), 1000Genomes rs545664320, ExAC rs545664320
- H3N (p.His3Asn), Ensembl rs2120079579
- H3P (p.His3Pro), 1000Genomes rs545664320, ExAC rs545664320, MetaLR 0.02, MetaSVM -1.01
- H3R (p.His3Arg), 1000Genomes rs545664320, ExAC rs545664320, REVEL 0.04, CADD 21.80
- H3Y (p.His3Tyr), Ensembl rs2120079579, REVEL 0.04, CADD 22.40
- H3Q (p.His3Gln), gnomAD 11-69641322-C-G, REVEL 0.02, MetaLR 0.01
- Q4* (p.Gln4Ter), Ensembl rs2120079618, CADD 37.00
- Q4E (p.Gln4Glu), Ensembl rs2120079618, REVEL 0.09, CADD 18.50
- Q4H (p.Gln4His), TOPMed rs1356268873, gnomAD rs1356268873, REVEL 0.13, CADD 24.10
- Q4L (p.Gln4Leu), Ensembl rs2120079633
- Q4R (p.Gln4Arg), cosmic curated COSV10809, Ensembl rs2120079633, MetaLR 0.02, MetaSVM -1.04
- Q4Q (p.Gln4Gln), rs1356268873, gnomAD 11-69641325-G-A, CADD 13.70
- L5H (p.Leu5His), Ensembl rs2120079658, MetaLR 0.13, MetaSVM -0.84
- L5L (p.Leu5Leu), rs1214959982, gnomAD 11-69641328-C-T, CADD 13.80
- L6P (p.Leu6Pro), cosmic curated COSV57119, Ensembl rs2120079700, MetaLR 0.09, MetaSVM -1.01
- L6L (p.Leu6Leu), rs141529781, gnomAD 11-69641329-C-T, CADD 13.90
- C7G (p.Cys7Gly), Ensembl rs993495966
- C7R (p.Cys7Arg), Ensembl rs993495966
- C7S (p.Cys7Ser), gnomAD rs1486252402, REVEL 0.40, CADD 28.70
- C7W (p.Cys7Trp), Ensembl rs2120079739, MetaLR 0.12, MetaSVM -0.83
- C7Y (p.Cys7Tyr), gnomAD rs1486252402, REVEL 0.44, CADD 29.50
- C7F (p.Cys7Phe), gnomAD 11-69641333-G-T, REVEL 0.49, MetaLR 0.12
- C7C (p.Cys7Cys), rs2120079739, gnomAD 11-69641334-C-T, CADD 15.80
- C8G (p.Cys8Gly), ExAC rs773884084, gnomAD rs773884084, REVEL 0.33, CADD 24.80
- C8S (p.Cys8Ser), ExAC rs773884084, gnomAD rs773884084, MetaLR 0.03, MetaSVM -1.09
- C8W (p.Cys8Trp), TOPMed rs1855696875, gnomAD rs1855696875, REVEL 0.25, CADD 24.00
- C8Y (p.Cys8Tyr), cosmic curated COSV10809, TOPMed rs1340132260, REVEL 0.35, CADD 25.50
- C8R (p.Cys8Arg), gnomAD 11-69641335-T-C, REVEL 0.35, MetaLR 0.04
- C8* (p.Cys8Ter), gnomAD 11-69641337-C-A, CADD 35.00
- C8C (p.Cys8Cys), rs1855696875, gnomAD 11-69641337-C-T, CADD 15.30
- E9D (p.Glu9Asp), cosmic curated COSV57121, Ensembl rs2120079793
- E9K (p.Glu9Lys), cosmic curated COSV57119, Ensembl rs2120079775
- E9Q (p.Glu9Gln), Ensembl rs2120079775, REVEL 0.28, CADD 30.00
- E9V (p.Glu9Val), Ensembl rs2120079786, MetaLR 0.05, MetaSVM -1.09
- E9E (p.Glu9Glu), rs2120079793, gnomAD 11-69641340-A-G, CADD 13.10
- V10G (p.Val10Gly), Ensembl rs2120079809, MetaLR 0.02, MetaSVM -1.01
- V10M (p.Val10Met), rs761266790, ExAC rs761266790, gnomAD rs761266790, REVEL 0.13, CADD 23.00, Variant assessed as somatic; moderate impact.
- V10L (p.Val10Leu), gnomAD 11-69641341-G-T, REVEL 0.14, MetaLR 0.02
- V10V (p.Val10Val), rs1378636232, gnomAD 11-69641343-G-A, CADD 14.90
- E11K (p.Glu11Lys), TOPMed rs1855697005, REVEL 0.24, CADD 24.00
- E11Q (p.Glu11Gln), cosmic curated COSV99919, TOPMed rs1855697005, MetaLR 0.03, MetaSVM -1.09
- T12I (p.Thr12Ile), cosmic curated COSV57122, Ensembl rs2120079839
- T12N (p.Thr12Asn), Ensembl rs2120079839, REVEL 0.12, CADD 20.60
- T12S (p.Thr12Ser), Ensembl rs2120079839, MetaLR 0.02, MetaSVM -1.05
- T12T (p.Thr12Thr), gnomAD 11-69641349-C-A, CADD 14.20
- I13L (p.Ile13Leu), Ensembl rs2120079856
- I13M (p.Ile13Met), cosmic curated COSV57122, Ensembl rs867052528
- I13N (p.Ile13Asn), Ensembl rs2120079868
- I13S (p.Ile13Ser), cosmic curated COSV10718, Ensembl rs2120079868
- I13T (p.Ile13Thr), Ensembl rs2120079868, REVEL 0.12, CADD 23.10
- I13V (p.Ile13Val), Ensembl rs2120079856, MetaLR 0.01, MetaSVM -0.94
- I13F (p.Ile13Phe), gnomAD 11-69641350-A-T, REVEL 0.13, MetaLR 0.02
- R14C (p.Arg14Cys), gnomAD rs1372181670, REVEL 0.15, CADD 23.60
- R14H (p.Arg14His), Ensembl rs2120079935
- R14P (p.Arg14Pro), Ensembl rs2120079935, MetaLR 0.02, MetaSVM -1.03
- R14S (p.Arg14Ser), gnomAD rs1372181670, REVEL 0.16, CADD 22.30
- R14G (p.Arg14Gly), gnomAD 11-69641353-C-G, REVEL 0.18, MetaLR 0.03
- R14R (p.Arg14Arg), gnomAD 11-69641355-C-T, CADD 15.90
- R15C (p.Arg15Cys), 1000Genomes rs557545630, REVEL 0.24, CADD 31.00
- R15H (p.Arg15His), Ensembl rs1590912368
- R15P (p.Arg15Pro), Ensembl rs1590912368, MetaLR 0.10, MetaSVM -0.94
- R15S (p.Arg15Ser), 1000Genomes rs557545630, REVEL 0.25, CADD 27.20
- R15R (p.Arg15Arg), rs767093177, gnomAD 11-69641358-C-A, CADD 14.80
- A16P (p.Ala16Pro), TOPMed rs1299107729
- A16S (p.Ala16Ser), rs1299107729, TOPMed rs1299107729, Variant assessed as somatic; moderate impact.
- A16T (p.Ala16Thr), TOPMed rs1299107729, REVEL 0.25, CADD 31.00
- A16V (p.Ala16Val), Ensembl rs2120079994, MetaLR 0.12, MetaSVM -0.86
- A16A (p.Ala16Ala), rs2120080004, gnomAD 11-69641361-G-C, CADD 14.20
- Y17D (p.Tyr17Asp), Ensembl rs2120080016
- Y17F (p.Tyr17Phe), Ensembl rs2120080028
- Y17H (p.Tyr17His), Ensembl rs2120080016
- Y17N (p.Tyr17Asn), Ensembl rs2120080016
- Y17S (p.Tyr17Ser), Ensembl rs2120080028, MetaLR 0.02, MetaSVM -1.07
- Y17C (p.Tyr17Cys), gnomAD 11-69641363-A-G, REVEL 0.24, MetaLR 0.03
- P18A (p.Pro18Ala), ExAC rs772857967, gnomAD rs772857967, REVEL 0.08, CADD 20.40
- P18H (p.Pro18His), Ensembl rs2120080068, MetaLR 0.02, MetaSVM -1.05
- P18L (p.Pro18Leu), NCI-TCGA Cosmic COSV5712, Ensembl rs2120080068, REVEL 0.07, CADD 21.40, Variant assessed as somatic; moderate impact.
- P18R (p.Pro18Arg), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57122, Ensembl rs2120080068, REVEL 0.10, CADD 18.90, Variant assessed as somatic; moderate impact.
- P18S (p.Pro18Ser), rs772857967, NCI-TCGA Cosmic COSV5712, cosmic curated COSV57121, ExAC rs772857967, REVEL 0.09, CADD 21.60, Variant assessed as somatic; moderate impact.
- D19A (p.Asp19Ala), Ensembl rs2120080100
- D19E (p.Asp19Glu), gnomAD rs1417631865, REVEL 0.24, CADD 25.10
- D19G (p.Asp19Gly), Ensembl rs2120080100
- D19H (p.Asp19His), Ensembl rs2120080084
- D19N (p.Asp19Asn), cosmic curated COSV10505, Ensembl rs2120080084, REVEL 0.36, CADD 32.00
- D19V (p.Asp19Val), Ensembl rs2120080100, MetaLR 0.11, MetaSVM -0.92
- D19Y (p.Asp19Tyr), Ensembl rs2120080084, REVEL 0.57, CADD 32.00
- D19D (p.Asp19Asp), rs1417631865, gnomAD 11-69641370-T-C, CADD 15.40
- A20D (p.Ala20Asp), NCI-TCGA TCGA novel, Ensembl rs2120080142, Variant assessed as somatic; moderate impact.
- A20P (p.Ala20Pro), Ensembl rs2120080130
- A20T (p.Ala20Thr), NCI-TCGA TCGA novel, Ensembl rs2120080130, REVEL 0.07, CADD 22.40, Variant assessed as somatic; moderate impact.
- A20V (p.Ala20Val), Ensembl rs2120080142, MetaLR 0.03, MetaSVM -1.04
- A20A (p.Ala20Ala), rs143734358, gnomAD 11-69641373-C-T, CADD 16.40
- N21D (p.Asn21Asp), rs766170770, NCI-TCGA Cosmic COSV9991, cosmic curated COSV99919, ExAC rs766170770, REVEL 0.15, CADD 23.20, Variant assessed as somatic; moderate impact.
- N21H (p.Asn21His), ExAC rs766170770, gnomAD rs766170770
- N21I (p.Asn21Ile), Ensembl rs1855697454
- N21K (p.Asn21Lys), Ensembl rs2120080193, REVEL 0.15, CADD 21.10
- N21S (p.Asn21Ser), Ensembl rs1855697454, REVEL 0.13, CADD 22.10
- N21T (p.Asn21Thr), Ensembl rs1855697454
- N21Y (p.Asn21Tyr), ExAC rs766170770, gnomAD rs766170770, MetaLR 0.06, MetaSVM -1.11
- N21N (p.Asn21Asn), rs2120080193, gnomAD 11-69641376-C-T, CADD 14.70
- L22F (p.Leu22Phe), Ensembl rs2120080218
- L22H (p.Leu22His), Ensembl rs2120080229
- L22P (p.Leu22Pro), Ensembl rs2120080229, MetaLR 0.10, MetaSVM -0.97
- L23F (p.Leu23Phe), ExAC rs753863475, gnomAD rs753863475, REVEL 0.16, CADD 23.80
- L23H (p.Leu23His), Ensembl rs2120080275
- L23I (p.Leu23Ile), ExAC rs753863475, gnomAD rs753863475
- L23V (p.Leu23Val), ExAC rs753863475, gnomAD rs753863475, MetaLR 0.07, MetaSVM -1.03
- L23del (p.Leu23del), rs1307164496, gnomAD 11-69641375-ACCT-, CADD 22.20
- L23L (p.Leu23Leu), rs1347957438, gnomAD 11-69641382-C-T, CADD 13.20
- N24D (p.Asn24Asp), Ensembl rs2120080301
- N24H (p.Asn24His), Ensembl rs2120080301, REVEL 0.12, CADD 24.50
- N24I (p.Asn24Ile), Ensembl rs2120080320
- N24K (p.Asn24Lys), gnomAD rs1301043705
- N24S (p.Asn24Ser), cosmic curated COSV57122, Ensembl rs2120080320
- N24T (p.Asn24Thr), NCI-TCGA Cosmic COSV5712, Ensembl rs2120080320, REVEL 0.08, CADD 22.60, Variant assessed as somatic; moderate impact.
- N24Y (p.Asn24Tyr), Ensembl rs2120080301, MetaLR 0.04, MetaSVM -1.10
- N24N (p.Asn24Asn), rs1301043705, gnomAD 11-69641385-C-T, CADD 15.10
- D25A (p.Asp25Ala), NCI-TCGA Cosmic COSV5711, cosmic curated COSV57119, gnomAD rs1400812649, Variant assessed as somatic; moderate impact.
- D25E (p.Asp25Glu), Ensembl rs2120080384
- D25G (p.Asp25Gly), gnomAD rs1400812649, REVEL 0.33, CADD 32.00
- D25H (p.Asp25His), Ensembl rs2120080356, REVEL 0.33, CADD 31.00
- D25N (p.Asp25Asn), Ensembl rs2120080356
- D25V (p.Asp25Val), gnomAD rs1400812649, MetaLR 0.07, MetaSVM -1.07
- D25Y (p.Asp25Tyr), gnomAD 11-69641386-G-T, REVEL 0.41, MetaLR 0.11
- R26G (p.Arg26Gly), Ensembl rs2120080399, Uncertain significance
- R26L (p.Arg26Leu), Ensembl rs2120080416, REVEL 0.56, CADD 32.00
- R26P (p.Arg26Pro), Ensembl rs2120080416
- R26Q (p.Arg26Gln), Ensembl rs2120080416
- R26W (p.Arg26Trp), Ensembl rs2120080399, MetaLR 0.19, MetaSVM -0.56, Uncertain significance, Congenital long QT syndrome
- R26R (p.Arg26Arg), rs2120080399, gnomAD 11-69641389-C-A, CADD 16.10
- V27E (p.Val27Glu), Ensembl rs2120080458
- V27G (p.Val27Gly), Ensembl rs2120080458
- V27M (p.Val27Met), Ensembl rs2120080449, MetaLR 0.15, MetaSVM -0.55
- V27V (p.Val27Val), rs2120080465, gnomAD 11-69641394-G-A, CADD 15.30
- L28P (p.Leu28Pro), Ensembl rs2120080492
- L28Q (p.Leu28Gln), Ensembl rs2120080492
- L28V (p.Leu28Val), ExAC rs776568792, gnomAD rs776568792, MetaLR 0.16, MetaSVM -0.67
- L28L (p.Leu28Leu), rs776568792, gnomAD 11-69641395-C-T, CADD 15.10
- R29G (p.Arg29Gly), Ensembl rs2120080526
- R29L (p.Arg29Leu), Ensembl rs2120080543
- R29P (p.Arg29Pro), Ensembl rs2120080543
- R29Q (p.Arg29Gln), Ensembl rs2120080543, REVEL 0.09, CADD 21.70
- R29W (p.Arg29Trp), Ensembl rs2120080526, MetaLR 0.05, MetaSVM -1.03
- R29R (p.Arg29Arg), rs751700485, gnomAD 11-69641400-G-A, CADD 15.20
- A30D (p.Ala30Asp), TOPMed rs1415272481, gnomAD rs1415272481, REVEL 0.19, CADD 26.30
- A30G (p.Ala30Gly), TOPMed rs1415272481, gnomAD rs1415272481
- A30P (p.Ala30Pro), ESP rs2220247, ExAC rs2220247, TOPMed rs2220247, gnomAD rs2220247, REVEL 0.22, CADD 27.80
- A30S (p.Ala30Ser), ESP rs2220247, ExAC rs2220247, TOPMed rs2220247, gnomAD rs2220247
- A30T (p.Ala30Thr), cosmic curated COSV57124, ESP rs2220247, ExAC rs2220247, TOPMed rs2220247, REVEL 0.09, CADD 22.70
- A30V (p.Ala30Val), TOPMed rs1415272481, gnomAD rs1415272481, MetaLR 0.03, MetaSVM -1.06
- A30A (p.Ala30Ala), rs781335332, gnomAD 11-69641403-C-T, CADD 16.40
- M31I (p.Met31Ile), cosmic curated COSV10505, Ensembl rs2120080674, REVEL 0.25, CADD 24.70
- M31K (p.Met31Lys), Ensembl rs2120080661
- M31L (p.Met31Leu), NCI-TCGA TCGA novel, Ensembl rs2120080647, Variant assessed as somatic; moderate impact.
- M31R (p.Met31Arg), Ensembl rs2120080661
- M31T (p.Met31Thr), Ensembl rs2120080661, MetaLR 0.13, MetaSVM -0.87
- L32M (p.Leu32Met), Ensembl rs2120080688
- L32P (p.Leu32Pro), Ensembl rs2120080702
- L32Q (p.Leu32Gln), Ensembl rs2120080702
- L32V (p.Leu32Val), Ensembl rs2120080688, MetaLR 0.11, MetaSVM -1.02
- L32R (p.Leu32Arg), gnomAD 11-69641408-T-G, REVEL 0.36, MetaLR 0.09
- K33* (p.Lys33Ter), Ensembl rs2120080708
- K33E (p.Lys33Glu), Ensembl rs2120080708
- K33M (p.Lys33Met), Ensembl rs2120080722
- K33N (p.Lys33Asn), Ensembl rs2120080736
- K33R (p.Lys33Arg), cosmic curated COSV10718, Ensembl rs2120080722, MetaLR 0.03, MetaSVM -1.08
- K33Q (p.Lys33Gln), gnomAD 11-69641410-A-C, REVEL 0.06, MetaLR 0.03
- A34E (p.Ala34Glu), Ensembl rs2120080769
- A34G (p.Ala34Gly), Ensembl rs2120080769
- A34P (p.Ala34Pro), Ensembl rs2120080751
- A34S (p.Ala34Ser), Ensembl rs2120080751
- A34T (p.Ala34Thr), Ensembl rs2120080751, REVEL 0.07, CADD 22.60
- A34V (p.Ala34Val), Ensembl rs2120080769, MetaLR 0.02, MetaSVM -1.06
- A34A (p.Ala34Ala), rs925185471, gnomAD 11-69641415-G-A, CADD 13.90
Public CCND1 analysis runs
- CCND1 analysis run — CCND1 (1,421 variants) — completed 2026-08-19