EED (Polycomb protein EED) variants and mutations
EED (also known as Polycomb protein EED) is a human protein-coding gene encoding a polycomb protein. Within Polycomb repressive complex 2, it recognizes H3K27 methylation to reinforce transcriptional silencing across chromatin. Germline pathogenic variants can cause Cohen-Gibson-like overgrowth phenotypes, while somatic alterations contribute to cancer. This analysis covers 654 EED variants and mutations. Of these, 67% have computational variant effect predictions. Disease context includes Cohen-Gibson syndrome, viral infectious disease, and smoking initiation. Example EED variants include M1?, S2A, and S2F.
Variant analysis overview
- Gene: EED
- Protein: Polycomb protein EED
- UniProt accession: O75530
- Organism: Homo sapiens
- Variants analyzed: 654
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 457 unspecified-consequence records; 55 synonymous variants; 10 frameshift variants; 116 missense variants; 8 stop-gained variants; 4 in-frame deletions; 1 in-frame insertions; 1 splice-region variants; 2 substitution
- Prediction scores: 436 variants have prediction scores (67% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Cohen-Gibson syndrome, viral infectious disease, smoking initiation, melanoma, breast carcinoma, cancer, Alzheimer disease, smoking behavior, attention deficit-hyperactivity disorder, substance abuse, cannabis dependence, autism spectrum disorder.
Protein structure and variant hotspots
- Protein features: 16 post-translational modification sites.
- PTM context: 31 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 EED variants
Examples include M1?, S2A, S2F, S2P, S2T, S2Y, S2W, S2L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10503
- S2A (p.Ser2Ala), ExAC rs745543096, TOPMed rs745543096, gnomAD rs745543096, REVEL 0.19, CADD 22.90, Uncertain significance
- S2F (p.Ser2Phe), cosmic curated COSV10455, TOPMed rs1371238695, gnomAD rs1371238695
- S2P (p.Ser2Pro), rs745543096, ClinGen CA6216276, ClinVar RCV002746438, ExAC rs745543096, REVEL 0.39, CADD 23.60, Uncertain significance, Cohen-Gibson syndrome
- S2T (p.Ser2Thr), ExAC rs745543096, TOPMed rs745543096, gnomAD rs745543096, REVEL 0.27, CADD 22.70, Uncertain significance
- S2Y (p.Ser2Tyr), TOPMed rs1371238695, gnomAD rs1371238695, REVEL 0.34, CADD 26.10
- S2W (p.Ser2Trp), rs1945351142, gnomAD 11-86245060-C-G, CADD 21.30
- S2L (p.Ser2Leu), gnomAD 11-86245060-C-T, CADD 21.60
- S2* (p.Ser2Ter), gnomAD 11-86245060-C-A, CADD 21.20
- S2S (p.Ser2Ser), gnomAD 11-86245061-G-A, CADD 20.90
- S2C (p.Ser2Cys), gnomAD 11-86245234-C-G, REVEL 0.28, CADD 26.70
- E3D (p.Glu3Asp), rs773510026, ExAC rs773510026, TOPMed rs773510026, gnomAD rs773510026, REVEL 0.26, CADD 26.90, Uncertain significance, Cohen-Gibson syndrome
- E3G (p.Glu3Gly), ExAC rs772576166, TOPMed rs772576166, gnomAD rs772576166, REVEL 0.33, CADD 32.00
- E3K (p.Glu3Lys), cosmic curated COSV54559, gnomAD rs1310112307
- E3Q (p.Glu3Gln), gnomAD rs1310112307, REVEL 0.24, CADD 31.00
- E3E (p.Glu3Glu), rs773510026, gnomAD 11-86245238-G-A, CADD 13.20
- R4G (p.Arg4Gly), ExAC rs761126162, gnomAD rs761126162, REVEL 0.34, CADD 25.00
- R4K (p.Arg4Lys), rs766472086, ClinGen CA382061035, ClinVar RCV001309293, ExAC rs766472086, REVEL 0.28, CADD 22.90, Uncertain significance, Cohen-Gibson syndrome
- R4M (p.Arg4Met), rs766472086, ClinGen CA6216283, cosmic curated COSV54553, ClinVar RCV002975899, REVEL 0.33, CADD 24.90, Uncertain significance, Cohen-Gibson syndrome; Inborn genetic diseases
- R4S (p.Arg4Ser), rs548903343, ExAC rs548903343, TOPMed rs548903343, gnomAD rs548903343, REVEL 0.30, CADD 24.30, Uncertain significance, Inborn genetic diseases
- R4C (p.Arg4Cys), gnomAD 11-86245068-C-T, CADD 20.80
- R4H (p.Arg4His), gnomAD 11-86245069-G-A, CADD 20.80
- R4P (p.Arg4Pro), gnomAD 11-86245069-G-C, CADD 20.50
- R4L (p.Arg4Leu), rs1945351931, gnomAD 11-86245069-G-T, CADD 20.40
- R4R (p.Arg4Arg), gnomAD 11-86245070-C-A, CADD 20.20
- R4W (p.Arg4Trp), rs1487935190, gnomAD 11-86245077-C-T, CADD 21.00
- R4Q (p.Arg4Gln), rs1402670100, gnomAD 11-86245078-G-A, CADD 21.10
- E5A (p.Glu5Ala), 1000Genomes rs557688582, ExAC rs557688582, gnomAD rs557688582, REVEL 0.21, CADD 22.50
- E5G (p.Glu5Gly), rs557688582, ClinGen CA382061041, ClinVar RCV002915928, REVEL 0.24, CADD 23.30, Uncertain significance, Inborn genetic diseases
- E5K (p.Glu5Lys), TOPMed rs1250649508, gnomAD rs1250649508, REVEL 0.24, CADD 23.40
- E5* (p.Glu5Ter), gnomAD 11-86245242-G-T, CADD 45.00
- E5D (p.Glu5Asp), gnomAD 11-86245244-A-T, REVEL 0.21, CADD 22.60
- E5E (p.Glu5Glu), gnomAD 11-86245244-A-G, CADD 14.70
- V6A (p.Val6Ala), rs752828124, ClinGen CA6216287, ClinVar RCV002038071, ExAC rs752828124, REVEL 0.19, CADD 22.50, Uncertain significance, Cohen-Gibson syndrome
- V6M (p.Val6Met), rs377098118, ClinGen CA6216286, ClinVar RCV002772865, ESP rs377098118, REVEL 0.22, CADD 22.80, Uncertain significance, Inborn genetic diseases
- V6L (p.Val6Leu), gnomAD 11-86245245-G-C, REVEL 0.20, CADD 22.60
- S7* (p.Ser7Ter), cosmic curated COSV99646, CADD 37.00
- S7L (p.Ser7Leu), ESP rs369888376, ExAC rs369888376, TOPMed rs369888376, gnomAD rs369888376, REVEL 0.19, CADD 24.00, Benign, not specified
- S7P (p.Ser7Pro), TOPMed rs1452371993, gnomAD rs1452371993, REVEL 0.26, CADD 22.50
- S7W (p.Ser7Trp), cosmic curated COSV54558
- S7del (p.Ser7del), gnomAD 11-86245246-TGTC-, CADD 20.20
- S7S (p.Ser7Ser), rs1191418992, gnomAD 11-86245250-G-T, CADD 13.00
- T8I (p.Thr8Ile), Ensembl rs372992816
- T8A (p.Thr8Ala), gnomAD 11-86245251-A-G, REVEL 0.17, CADD 19.50
- T8T (p.Thr8Thr), rs1945360963, gnomAD 11-86245253-T-C, CADD 12.40
- A9E (p.Ala9Glu), ExAC rs751356706, gnomAD rs751356706, REVEL 0.14, CADD 21.80
- A9S (p.Ala9Ser), ESP rs374657922, ExAC rs374657922, TOPMed rs374657922, gnomAD rs374657922, REVEL 0.16, CADD 19.40
- A9T (p.Ala9Thr), ESP rs374657922, ExAC rs374657922, TOPMed rs374657922, gnomAD rs374657922
- A9V (p.Ala9Val), ExAC rs751356706, gnomAD rs751356706, REVEL 0.16, CADD 21.70
- A9A (p.Ala9Ala), rs1294279232, gnomAD 11-86245055-G-C, CADD 21.10
- A9G (p.Ala9Gly), gnomAD 11-86245255-C-G, REVEL 0.13, CADD 22.40
- P10A (p.Pro10Ala), cosmic curated COSV54557, REVEL 0.15, CADD 20.00
- P10L (p.Pro10Leu), rs780894846, NCI-TCGA Cosmic COSV9964, ExAC rs780894846, TOPMed rs780894846, REVEL 0.16, CADD 24.00, Variant assessed as somatic; moderate impact.
- P10Q (p.Pro10Gln), ExAC rs780894846, TOPMed rs780894846, gnomAD rs780894846
- P10R (p.Pro10Arg), rs780894846, NCI-TCGA Cosmic COSV9964, cosmic curated COSV99646, ExAC rs780894846, REVEL 0.13, CADD 24.30, Uncertain significance, Inborn genetic diseases
- P10S (p.Pro10Ser), cosmic curated COSV54557, TOPMed rs1046364358, gnomAD rs1046364358, REVEL 0.15, CADD 22.00
- P10T (p.Pro10Thr), rs1348161963, gnomAD 11-86245059-T-TCG, CADD 20.90
- P10P (p.Pro10Pro), rs1362025654, gnomAD 11-86245073-G-A, CADD 20.90
- A11E (p.Ala11Glu), ExAC rs745525077, gnomAD rs745525077, REVEL 0.44, CADD 26.00
- A11P (p.Ala11Pro), Ensembl rs200506006
- A11V (p.Ala11Val), ExAC rs745525077, gnomAD rs745525077, REVEL 0.16, CADD 24.40
- A11G (p.Ala11Gly), gnomAD 11-86245261-C-G, REVEL 0.29, CADD 25.00
- A11A (p.Ala11Ala), gnomAD 11-86245262-G-T, CADD 14.60
- G12A (p.Gly12Ala), TOPMed rs907459561, REVEL 0.16, CADD 22.80
- G12E (p.Gly12Glu), TOPMed rs907459561, REVEL 0.32, CADD 27.20
- G12R (p.Gly12Arg), TOPMed rs1240623101, gnomAD rs1240623101, REVEL 0.37, CADD 26.20
- G12V (p.Gly12Val), TOPMed rs907459561, REVEL 0.34, CADD 26.90
- G12G (p.Gly12Gly), gnomAD 11-86245058-G-C, CADD 20.60
- G12C (p.Gly12Cys), gnomAD 11-86245086-G-T, CADD 21.50
- G12S (p.Gly12Ser), rs1945352860, gnomAD 11-86245086-G-A, CADD 21.80
- G12W (p.Gly12Trp), rs897916992, gnomAD 11-86245104-G-T, CADD 21.00
- G12D (p.Gly12Asp), rs527999615, gnomAD 11-86245111-G-A, CADD 20.90
- G12* (p.Gly12Ter), gnomAD 11-86245116-G-T, CADD 20.80
- T13I (p.Thr13Ile), ExAC rs772521195, TOPMed rs772521195, gnomAD rs772521195, REVEL 0.15, CADD 23.60
- T13K (p.Thr13Lys), ExAC rs772521195, TOPMed rs772521195, gnomAD rs772521195
- T13A (p.Thr13Ala), gnomAD 11-86245266-A-G, REVEL 0.21, CADD 22.50
- T13T (p.Thr13Thr), rs773741012, gnomAD 11-86245268-A-G, CADD 14.30
- D14E (p.Asp14Glu), gnomAD rs1416891719, REVEL 0.19, CADD 16.40
- D14H (p.Asp14His), TOPMed rs1294600154, gnomAD rs1294600154, REVEL 0.25, CADD 29.60
- D14N (p.Asp14Asn), TOPMed rs1294600154, gnomAD rs1294600154, REVEL 0.27, CADD 26.10
- D14Y (p.Asp14Tyr), gnomAD 11-86245098-G-T, CADD 21.40
- D14G (p.Asp14Gly), gnomAD 11-86245099-A-G, CADD 22.10
- D14A (p.Asp14Ala), gnomAD 11-86245099-A-C, CADD 22.00
- D14D (p.Asp14Asp), rs1314257518, gnomAD 11-86245100-C-T, CADD 21.60
- M15I (p.Met15Ile), ExAC rs202211864, TOPMed rs202211864, gnomAD rs202211864, REVEL 0.17, CADD 22.10, Uncertain significance, Inborn genetic diseases
- M15K (p.Met15Lys), TOPMed rs1200518953, gnomAD rs1200518953, Uncertain significance
- M15L (p.Met15Leu), 1000Genomes rs200782451, ESP rs200782451, ExAC rs200782451, TOPMed rs200782451, REVEL 0.17, CADD 22.60, Uncertain significance
- M15R (p.Met15Arg), rs1200518953, ClinGen CA382061092, ClinVar RCV001976246, TOPMed rs1200518953, REVEL 0.30, CADD 24.40, Uncertain significance, Cohen-Gibson syndrome
- M15V (p.Met15Val), rs200782451, ClinGen CA6216299, ClinVar RCV003248201, 1000Genomes rs200782451, REVEL 0.20, CADD 20.90, Uncertain significance, Inborn genetic diseases
- P16L (p.Pro16Leu), ESP rs371991859, ExAC rs371991859, gnomAD rs371991859, REVEL 0.34, CADD 27.60, Uncertain significance, Cohen-Gibson syndrome
- P16S (p.Pro16Ser), Ensembl rs1406291188, REVEL 0.26, CADD 23.80
- P16P (p.Pro16Pro), rs1218882175, gnomAD 11-86245277-T-A, CADD 14.60
- A17E (p.Ala17Glu), TOPMed rs1945363239, REVEL 0.22, CADD 22.20, Uncertain significance
- A17G (p.Ala17Gly), TOPMed rs1945363239, REVEL 0.14, CADD 22.50, Uncertain significance
- A17S (p.Ala17Ser), cosmic curated COSV10584, REVEL 0.14, CADD 21.10
- A17V (p.Ala17Val), rs1945363239, ClinGen CA382061105, ClinVar RCV001258333, ClinVar RCV003393928, REVEL 0.14, CADD 22.30, Uncertain significance, Cohen-Gibson syndrome; not provided
- A17A (p.Ala17Ala), rs759736352, gnomAD 11-86245280-G-T, CADD 13.00
- A18G (p.Ala18Gly), TOPMed rs1945363445, REVEL 0.19, CADD 23.20
- A18T (p.Ala18Thr), cosmic curated COSV54553
- A18V (p.Ala18Val), gnomAD 11-86245282-C-T, REVEL 0.19, CADD 21.60
- K19R (p.Lys19Arg), 1000Genomes rs199943809, ExAC rs199943809, TOPMed rs199943809, gnomAD rs199943809, REVEL 0.38, CADD 25.70
- K19K (p.Lys19Lys), gnomAD 11-86245286-G-A, CADD 14.40
- K20K (p.Lys20Lys), gnomAD 11-86245289-G-A, CADD 13.60
- Q21H (p.Gln21His), rs1186239339, gnomAD rs1186239339, REVEL 0.37, CADD 23.80, Variant assessed as somatic; moderate impact.
- Q21P (p.Gln21Pro), TOPMed rs1945363684
- Q21R (p.Gln21Arg), TOPMed rs1945363684, REVEL 0.42, CADD 24.70
- Q21* (p.Gln21Ter), gnomAD 11-86245203-C-T, CADD 20.50
- Q21Q (p.Gln21Gln), rs1229395776, gnomAD 11-86245205-G-A, CADD 20.90
- K22N (p.Lys22Asn), ExAC rs763154303, TOPMed rs763154303, gnomAD rs763154303, REVEL 0.39, CADD 24.20
- K22R (p.Lys22Arg), ExAC rs775661038, TOPMed rs775661038, gnomAD rs775661038, REVEL 0.38, CADD 23.80
- K22K (p.Lys22Lys), rs763154303, gnomAD 11-86245295-G-A, CADD 14.30
- L23L (p.Leu23Leu), gnomAD 11-86245083-C-T, CADD 21.20
- L23M (p.Leu23Met), gnomAD 11-86245083-C-A, CADD 20.90
- L23P (p.Leu23Pro), gnomAD 11-86245297-T-C, REVEL 0.53, CADD 23.60
- S24G (p.Ser24Gly), ExAC rs751488435, TOPMed rs751488435, gnomAD rs751488435, REVEL 0.34, CADD 24.90, Uncertain significance, Inborn genetic diseases
- S24C (p.Ser24Cys), rs1302284830, gnomAD 11-86245101-A-T, CADD 21.80
- S24R (p.Ser24Arg), gnomAD 11-86245101-A-AG, CADD 20.70
- S24I (p.Ser24Ile), gnomAD 11-86245102-G-T, CADD 20.20
- S24N (p.Ser24Asn), gnomAD 11-86245102-G-A, CADD 20.60
- S24S (p.Ser24Ser), gnomAD 11-86245301-C-T, CADD 14.20
- S25G (p.Ser25Gly), rs1459981515, ClinGen CA382061154, ClinVar RCV001197531, TOPMed rs1459981515, REVEL 0.23, CADD 24.30, Uncertain significance, Cohen-Gibson syndrome
- D26E (p.Asp26Glu), cosmic curated COSV54556, REVEL 0.18, CADD 17.70
- D26N (p.Asp26Asn), ExAC rs757195252, TOPMed rs757195252, gnomAD rs757195252, REVEL 0.27, CADD 24.10
- D26G (p.Asp26Gly), gnomAD 11-86245306-A-G, REVEL 0.42, CADD 25.30
- D26D (p.Asp26Asp), rs140683797, gnomAD 11-86245307-C-T, CADD 13.20
- E27D (p.Glu27Asp), cosmic curated COSV54559
- E27G (p.Glu27Gly), Ensembl rs1945364537
- E27K (p.Glu27Lys), Ensembl rs1945364422
- E27E (p.Glu27Glu), rs554137878, gnomAD 11-86245310-G-A, CADD 13.20
- N28K (p.Asn28Lys), gnomAD rs1288069188, REVEL 0.44, CADD 25.10
- N28I (p.Asn28Ile), gnomAD 11-86245312-A-T, REVEL 0.47, CADD 28.70
- S29G (p.Ser29Gly), gnomAD rs1945364878, REVEL 0.40, CADD 22.80
- S29N (p.Ser29Asn), NCI-TCGA Cosmic COSV5455, cosmic curated COSV54553, Variant assessed as somatic; moderate impact.
- S29T (p.Ser29Thr), gnomAD rs1371470025, REVEL 0.22, CADD 22.60
- p.Ser28 Gly29del, gnomAD 11-86245125-GGCGG, CADD 20.50
- S29R (p.Ser29Arg), gnomAD 11-86245131-A-C, CADD 16.70
- S29C (p.Ser29Cys), gnomAD 11-86245131-A-T, CADD 16.60
- S29I (p.Ser29Ile), gnomAD 11-86245132-G-T, CADD 16.30
- S29S (p.Ser29Ser), rs1038718876, gnomAD 11-86245133-C-T, CADD 8.43
- N30I (p.Asn30Ile), ESP rs145674802, ExAC rs145674802, gnomAD rs145674802, REVEL 0.59, CADD 24.30
- N30T (p.Asn30Thr), gnomAD 11-86245138-A-C, CADD 14.50
- N30S (p.Asn30Ser), gnomAD 11-86245318-A-G, REVEL 0.34, CADD 22.40
- P31A (p.Pro31Ala), TOPMed rs1945365108
- P31L (p.Pro31Leu), cosmic curated COSV10503
- P31Q (p.Pro31Gln), cosmic curated COSV99646
- P31P (p.Pro31Pro), gnomAD 11-86245322-A-C, CADD 7.93
- D32G (p.Asp32Gly), TOPMed rs1945365201, REVEL 0.60, CADD 25.40
- D32D (p.Asp32Asp), rs779705890, gnomAD 11-86245325-C-T, CADD 13.00
- D32E (p.Asp32Glu), gnomAD 11-86245325-C-A, REVEL 0.22, CADD 19.10
- L33F (p.Leu33Phe), ExAC rs748759009, TOPMed rs748759009, gnomAD rs748759009, REVEL 0.15, CADD 20.70
- L33V (p.Leu33Val), ExAC rs748759009, TOPMed rs748759009, gnomAD rs748759009, REVEL 0.17, CADD 19.40
- L33* (p.Leu33Ter), rs1342200275, gnomAD 11-86245168-T-A, CADD 21.50
- L33W (p.Leu33Trp), rs1342200275, gnomAD 11-86245168-T-G, CADD 21.60
- L33L (p.Leu33Leu), rs1313613557, gnomAD 11-86245328-C-T, CADD 9.59
- S34C (p.Ser34Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S34I (p.Ser34Ile), gnomAD 11-86245150-G-T, CADD 20.30
- S34N (p.Ser34Asn), gnomAD 11-86245150-G-A, CADD 20.70
- S34T (p.Ser34Thr), gnomAD 11-86245150-G-C, CADD 20.40
- S34R (p.Ser34Arg), gnomAD 11-86245151-C-A, CADD 20.20
- S34S (p.Ser34Ser), gnomAD 11-86245151-C-T, CADD 20.70
- S34W (p.Ser34Trp), gnomAD 11-86245153-C-G, CADD 19.90
- S34L (p.Ser34Leu), gnomAD 11-86245153-C-T, CADD 20.30
- S34* (p.Ser34Ter), gnomAD 11-86245153-C-A, CADD 19.80
- S34E (p.Ser34Glu), gnomAD 11-86245324-ACCTC, CADD 32.00
- S34P (p.Ser34Pro), gnomAD 11-86245329-T-C, REVEL 0.46, CADD 31.00
- G35E (p.Gly35Glu), NCI-TCGA Cosmic COSV5455, cosmic curated COSV54555, Variant assessed as somatic; moderate impact.
- p.Gly24 Gly27del, gnomAD 11-86245101-AGTGG, CADD 20.40
- G35S (p.Gly35Ser), gnomAD 11-86245119-G-A, CADD 20.00
- G35C (p.Gly35Cys), gnomAD 11-86245119-G-T, CADD 19.60
- G35V (p.Gly35Val), gnomAD 11-86245120-G-T, CADD 19.60
- G35D (p.Gly35Asp), gnomAD 11-86245120-G-A, CADD 19.90
- p.Gly27dup, rs1945354482, gnomAD 11-86245121-T-TGG, CADD 20.90
- G35G (p.Gly35Gly), gnomAD 11-86245121-T-C, CADD 21.50
- G35A (p.Gly35Ala), gnomAD 11-86245129-G-C, CADD 20.10
- D36E (p.Asp36Glu), TOPMed rs1226072986, gnomAD rs1226072986, REVEL 0.36, CADD 22.40, Uncertain significance, Inborn genetic diseases
- D36L (p.Asp36Leu), gnomAD 11-86245334-A-ATT, CADD 33.00
- D36G (p.Asp36Gly), gnomAD 11-86245336-A-G, REVEL 0.69, CADD 25.70
- D36D (p.Asp36Asp), gnomAD 11-86245337-C-T, CADD 13.10
- E37D (p.Glu37Asp), ExAC rs778444231, gnomAD rs778444231, REVEL 0.27, CADD 20.50
- N38K (p.Asn38Lys), NCI-TCGA Cosmic COSV5455, cosmic curated COSV54553, Variant assessed as somatic; moderate impact.
Public EED analysis runs
- EED analysis run — EED (654 variants) — completed 2026-08-22