CCR5 (C-C chemokine receptor type 5) variants and mutations
CCR5 (also known as C-C chemokine receptor type 5) is a human protein-coding gene encoding a c-C chemokine receptor type 5 protein. It directs migration of immune cells toward inflammatory chemokines and serves as a major coreceptor for entry of R5-tropic HIV-1. Homozygosity for the CCR5-delta32 deletion strongly reduces susceptibility to these HIV strains, and pharmacologic CCR5 blockade can inhibit viral entry. This analysis covers 941 CCR5 variants and mutations. Of these, 88% have computational variant effect predictions. Disease context includes HIV infectious disease, HIV-1 infection, and COVID-19. Example CCR5 variants include M1?, D2E, and D2N.
Variant analysis overview
- Gene: CCR5
- Protein: C-C chemokine receptor type 5
- UniProt accession: P51681
- Organism: Homo sapiens
- Variants analyzed: 941
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 559 unspecified-consequence records; 149 missense variants; 175 synonymous variants; 34 frameshift variants; 8 stop-gained variants; 9 in-frame deletions; 1 in-frame insertions; 1 protein altering variant; 1 stop lost; 4 substitution
- Prediction scores: 824 variants have prediction scores (88% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: HIV infectious disease, HIV-1 infection, COVID-19, viral infectious disease, type 1 diabetes mellitus, AIDS, chronic obstructive pulmonary disease, pneumonia, ulcerative colitis, Stroke, Cognitive impairment, HIV-associated neurocognitive disorder.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 10 post-translational modification sites.
- Structural context: 430 variants have structural context.
- PTM context: 30 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 CCR5 variants
Examples include M1?, D2E, D2N, D2Y, D2V, D2G, D2D, Y3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, NCI-TCGA Cosmic COSV9943, cosmic curated COSV99433, Variant assessed as somatic; high impact.
- D2E (p.Asp2Glu), gnomAD rs1365309969, REVEL 0.07, CADD 0.28
- D2N (p.Asp2Asn), gnomAD rs1165883785, REVEL 0.16, CADD 20.20
- D2Y (p.Asp2Tyr), gnomAD rs1165883785
- D2V (p.Asp2Val), gnomAD 3-46372907-A-T, REVEL 0.28, CADD 24.10
- D2G (p.Asp2Gly), gnomAD 3-46372907-A-G, REVEL 0.09, CADD 22.90
- D2D (p.Asp2Asp), rs1365309969, gnomAD 3-46372908-T-C, CADD 1.24
- Y3N (p.Tyr3Asn), Ensembl rs1701682906, REVEL 0.04, CADD 10.50
- Q4E (p.Gln4Glu), cosmic curated COSV52751, Ensembl rs748244565, REVEL 0.06, CADD 0.66
- Q4R (p.Gln4Arg), rs745912425, gnomAD 3-46372912-CAA-C, CADD 21.50
- Q4K (p.Gln4Lys), gnomAD 3-46372912-C-A, REVEL 0.05, CADD 2.36
- V5G (p.Val5Gly), ExAC rs766432600, gnomAD rs766432600, REVEL 0.07, CADD 8.44
- V5M (p.Val5Met), ExAC rs763192695, REVEL 0.05, CADD 10.80
- V5L (p.Val5Leu), gnomAD 3-46372915-G-C, REVEL 0.04, CADD 7.29
- V5E (p.Val5Glu), gnomAD 3-46372916-T-A, REVEL 0.05, CADD 4.50
- S6P (p.Ser6Pro), TOPMed rs1159424333, REVEL 0.12, CADD 0.23
- S6* (p.Ser6Ter), gnomAD 3-46372919-C-G, CADD 34.00
- S7N (p.Ser7Asn), Ensembl rs1701683359
- S7G (p.Ser7Gly), gnomAD 3-46372921-A-G, REVEL 0.05, CADD 15.50
- S7S (p.Ser7Ser), gnomAD 3-46372923-T-C, CADD 5.00
- P8L (p.Pro8Leu), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, Variant assessed as somatic; moderate impact.
- P8Q (p.Pro8Gln), rs868367428, NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, AlphaMissense 0.12, MetaLR 0.39, Variant assessed as somatic; moderate impact.
- P8T (p.Pro8Thr), Ensembl rs2106745879, REVEL 0.05, CADD 0.75
- Y10C (p.Tyr10Cys), gnomAD rs1351407662, REVEL 0.32, CADD 22.70
- Y10D (p.Tyr10Asp), UniProt VAR 003481, REVEL 0.20, CADD 12.40, Uncertain significance, in INCCR5-71A
- Y10Y (p.Tyr10Tyr), gnomAD 3-46372932-T-C, CADD 3.24
- D11G (p.Asp11Gly), ExAC rs751603911, TOPMed rs751603911, gnomAD rs751603911, REVEL 0.19, CADD 17.30
- D11del (p.Asp11del), gnomAD 3-46372932-TGAC-T, CADD 8.92
- D11V (p.Asp11Val), gnomAD 3-46372934-A-T, REVEL 0.35, CADD 17.10
- D11A (p.Asp11Ala), gnomAD 3-46372934-A-C, REVEL 0.30, CADD 17.60
- I12L (p.Ile12Leu), UniProt VAR 024066
- I12S (p.Ile12Ser), ExAC rs781613165, gnomAD rs781613165, REVEL 0.13, CADD 6.48
- I12T (p.Ile12Thr), ExAC rs781613165, gnomAD rs781613165, REVEL 0.13, CADD 4.08
- I12V (p.Ile12Val), ExAC rs755442066, gnomAD rs755442066, REVEL 0.07, CADD 0.03
- N13D (p.Asn13Asp), ExAC rs753095965, gnomAD rs753095965, REVEL 0.19, CADD 13.60
- N13S (p.Asn13Ser), gnomAD rs1701683755, REVEL 0.26, CADD 19.40
- Y14* (p.Tyr14Ter), gnomAD 3-46372944-T-G, CADD 26.70
- Y14Y (p.Tyr14Tyr), gnomAD 3-46372944-T-C, CADD 0.99
- Y15C (p.Tyr15Cys), ExAC rs777539326, gnomAD rs777539326, REVEL 0.05, CADD 4.75
- Y15H (p.Tyr15His), 1000Genomes rs200209014, ExAC rs200209014, TOPMed rs200209014, REVEL 0.03, CADD 1.76
- Y15del (p.Tyr15del), gnomAD 3-46372939-AATT-A, CADD 16.60
- Y15I (p.Tyr15Ile), rs758662716, gnomAD 3-46372943-AT-A, CADD 11.20
- Y15L (p.Tyr15Leu), rs1559567779, gnomAD 3-46372945-TA-T, CADD 9.10
- Y15Y (p.Tyr15Tyr), rs1220058040, gnomAD 3-46372947-T-C, CADD 0.07
- T16I (p.Thr16Ile), gnomAD rs1276255995, REVEL 0.06, CADD 0.00
- T16K (p.Thr16Lys), gnomAD 3-46372949-C-A, REVEL 0.07, CADD 0.00
- T16T (p.Thr16Thr), rs1438064610, gnomAD 3-46372950-A-G, CADD 1.49
- S17* (p.Ser17Ter), ESP rs369206494, ExAC rs369206494, TOPMed rs369206494, gnomAD rs369206494, CADD 33.00
- S17L (p.Ser17Leu), cosmic curated COSV99433, ESP rs369206494, ExAC rs369206494, TOPMed rs369206494, REVEL 0.14, CADD 13.60
- S17W (p.Ser17Trp), cosmic curated COSV52752, ESP rs369206494, ExAC rs369206494, TOPMed rs369206494, REVEL 0.15, CADD 19.30
- S17T (p.Ser17Thr), gnomAD 3-46372951-T-A, REVEL 0.07, CADD 0.42
- S17S (p.Ser17Ser), rs770002247, gnomAD 3-46372953-G-A, CADD 1.44
- E18K (p.Glu18Lys), cosmic curated COSV10609, ESP rs142904831, ExAC rs142904831, TOPMed rs142904831, REVEL 0.10, CADD 10.10, Uncertain significance, not specified
- E18E (p.Glu18Glu), gnomAD 3-46372956-G-A, CADD 2.95
- P19R (p.Pro19Arg), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52753, Variant assessed as somatic; moderate impact.
- P19T (p.Pro19Thr), cosmic curated COSV52752, REVEL 0.42, CADD 23.40
- P19P (p.Pro19Pro), rs1701684705, gnomAD 3-46372959-C-T, CADD 8.05
- C20* (p.Cys20Ter), ExAC rs760428955, TOPMed rs760428955, gnomAD rs760428955, CADD 27.20
- C20S (p.Cys20Ser), rs145061115, UniProt VAR 024067, 1000Genomes rs145061115, ESP rs145061115, REVEL 0.50, CADD 24.60
- C20G (p.Cys20Gly), gnomAD 3-46372960-T-G, REVEL 0.53, CADD 25.10
- C20R (p.Cys20Arg), gnomAD 3-46372960-T-C, REVEL 0.59, CADD 25.30
- Q21* (p.Gln21Ter), Ensembl rs1032906612
- K22* (p.Lys22Ter), ExAC rs768398484, TOPMed rs768398484, gnomAD rs768398484, CADD 34.00
- K22T (p.Lys22Thr), ExAC rs776432250, gnomAD rs776432250, REVEL 0.19, CADD 21.40
- I23N (p.Ile23Asn), cosmic curated COSV10962
- I23S (p.Ile23Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- I23V (p.Ile23Val), Ensembl rs1701685087
- I23I (p.Ile23Ile), rs763103073, gnomAD 3-46372971-C-A, CADD 0.68
- N24S (p.Asn24Ser), gnomAD rs1327148775, REVEL 0.03, CADD 2.40
- N24D (p.Asn24Asp), gnomAD 3-46372972-A-G, REVEL 0.12, CADD 0.00
- N24N (p.Asn24Asn), rs766509880, gnomAD 3-46372974-T-C, CADD 0.19
- V25E (p.Val25Glu), rs751650495, ClinGen CA2354555, ClinVar RCV003410720, ClinVar RCV004897803, REVEL 0.21, CADD 20.30, Uncertain significance, not specified
- V25M (p.Val25Met), gnomAD 3-46372975-G-A, REVEL 0.25, CADD 23.70
- V25V (p.Val25Val), rs759590067, gnomAD 3-46372977-G-A, CADD 6.37
- K26R (p.Lys26Arg), 1000Genomes rs189601230, ExAC rs189601230, TOPMed rs189601230, gnomAD rs189601230, REVEL 0.02, CADD 6.24
- K26K (p.Lys26Lys), rs1474984223, gnomAD 3-46372980-G-A, CADD 0.44
- Q27K (p.Gln27Lys), gnomAD 3-46372981-C-A, REVEL 0.03, MetaLR 0.08
- I28V (p.Ile28Val), gnomAD 3-46372984-A-G, REVEL 0.03, MetaLR 0.10
- I28I (p.Ile28Ile), rs753300247, gnomAD 3-46372986-C-T, CADD 0.09
- A29P (p.Ala29Pro), ESP rs1800939, ExAC rs1800939, TOPMed rs1800939, gnomAD rs1800939
- A29S (p.Ala29Ser), rs1800939, UniProt VAR 011839, ESP rs1800939, ExAC rs1800939, REVEL 0.10, CADD 17.30
- A29T (p.Ala29Thr), rs1800939, NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, ESP rs1800939, REVEL 0.21, CADD 18.90, Variant assessed as somatic; moderate impact.
- A29V (p.Ala29Val), TOPMed rs1701685601, gnomAD rs1701685601, REVEL 0.16, CADD 14.20
- A30D (p.Ala30Asp), TOPMed rs1701685697, REVEL 0.23, CADD 21.50
- A30T (p.Ala30Thr), TOPMed rs1389766324
- A30V (p.Ala30Val), gnomAD 3-46372991-C-T, REVEL 0.19, MetaLR 0.16
- R31C (p.Arg31Cys), TOPMed rs777944058, gnomAD rs777944058, REVEL 0.06, CADD 8.42
- R31H (p.Arg31His), rs56340326, ClinGen CA2354561, cosmic curated COSV10962, ClinVar RCV004183980, REVEL 0.05, CADD 0.00, Uncertain significance, not specified
- R31P (p.Arg31Pro), 1000Genomes rs56340326, ESP rs56340326, ExAC rs56340326, TOPMed rs56340326, REVEL 0.19, CADD 0.02, Uncertain significance, in INCCR5-72A
- R31R (p.Arg31Arg), rs1406813393, gnomAD 3-46372995-C-T, CADD 0.86
- L32F (p.Leu32Phe), ESP rs374426321, ExAC rs374426321, TOPMed rs374426321, gnomAD rs374426321, REVEL 0.10, CADD 7.29
- L32P (p.Leu32Pro), gnomAD 3-46372997-T-C, REVEL 0.50, MetaLR 0.31
- L33L (p.Leu33Leu), gnomAD 3-46373001-G-A, CADD 6.61
- P34L (p.Pro34Leu), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, UniProt VAR 003483, Uncertain significance, in TZCCR5-179
- P34S (p.Pro34Ser), gnomAD 3-46373002-C-T, REVEL 0.43, MetaLR 0.27
- P35L (p.Pro35Leu), ExAC rs745372153, TOPMed rs745372153, gnomAD rs745372153, REVEL 0.20, CADD 16.90
- P35S (p.Pro35Ser), ExAC rs778497859, gnomAD rs778497859, REVEL 0.16, CADD 22.00
- P35P (p.Pro35Pro), gnomAD 3-46373007-G-T, CADD 0.41
- L36L (p.Leu36Leu), gnomAD 3-46373010-C-G, CADD 7.18
- Y37C (p.Tyr37Cys), gnomAD 3-46373012-A-G, REVEL 0.43, MetaLR 0.33
- Y37* (p.Tyr37Ter), gnomAD 3-46373013-C-G, CADD 34.00
- S38L (p.Ser38Leu), gnomAD rs1443351351, REVEL 0.20, CADD 22.90
- S38S (p.Ser38Ser), rs1379360638, gnomAD 3-46373016-A-C, CADD 0.38
- L39M (p.Leu39Met), Ensembl rs1186533878
- L39P (p.Leu39Pro), ExAC rs779570167, TOPMed rs779570167, gnomAD rs779570167, REVEL 0.51, CADD 25.00, Uncertain significance
- L39R (p.Leu39Arg), rs779570167, ClinGen CA352469252, ClinVar RCV004189470, ExAC rs779570167, REVEL 0.51, CADD 24.70, Uncertain significance, not specified
- L39L (p.Leu39Leu), gnomAD 3-46373017-C-T, CADD 4.16
- V40M (p.Val40Met), gnomAD 3-46373020-G-A, REVEL 0.25, MetaLR 0.30
- V40V (p.Val40Val), gnomAD 3-46373022-G-A, CADD 4.99
- F41L (p.Phe41Leu), gnomAD 3-46373023-T-C, REVEL 0.13, MetaLR 0.33
- I42F (p.Ile42Phe), rs1475319259, UniProt VAR 024068, gnomAD rs1475319259, REVEL 0.25, CADD 22.20
- I42V (p.Ile42Val), gnomAD 3-46373026-A-G, REVEL 0.19, MetaLR 0.07
- I42N (p.Ile42Asn), gnomAD 3-46373027-T-A, REVEL 0.26, MetaLR 0.26
- F43L (p.Phe43Leu), TOPMed rs1701686546
- F43S (p.Phe43Ser), gnomAD 3-46373030-T-C, REVEL 0.02, MetaLR 0.08
- G44S (p.Gly44Ser), gnomAD 3-46373032-G-A, REVEL 0.48, MetaLR 0.44
- F45S (p.Phe45Ser), Ensembl rs1559567874, REVEL 0.09, CADD 19.70
- F45V (p.Phe45Val), cosmic curated COSV10808
- V46M (p.Val46Met), cosmic curated COSV10462, 1000Genomes rs41425744, ESP rs41425744, ExAC rs41425744, REVEL 0.18, CADD 20.50
- V46G (p.Val46Gly), gnomAD 3-46373039-T-G, REVEL 0.24, MetaLR 0.26
- V46V (p.Val46Val), rs776341341, gnomAD 3-46373040-G-A, CADD 10.90
- G47D (p.Gly47Asp), NCI-TCGA Cosmic COSV9943, cosmic curated COSV99433, Variant assessed as somatic; moderate impact.
- G47S (p.Gly47Ser), gnomAD 3-46373041-G-A, REVEL 0.67, MetaLR 0.54
- G47G (p.Gly47Gly), rs747999011, gnomAD 3-46373043-C-A, CADD 3.92
- N48D (p.Asn48Asp), gnomAD rs1299467349, REVEL 0.94, CADD 25.30
- N48K (p.Asn48Lys), gnomAD rs1405206791, REVEL 0.72, CADD 23.50
- N48S (p.Asn48Ser), cosmic curated COSV10462, 1000Genomes rs531662647, ExAC rs531662647, gnomAD rs531662647, REVEL 0.93, CADD 24.50
- N48Q (p.Asn48Gln), gnomAD 3-46373039-T-TG, CADD 24.80
- M49I (p.Met49Ile), ExAC rs759632621, gnomAD rs759632621, REVEL 0.04, CADD 4.18
- M49K (p.Met49Lys), ExAC rs774482480, TOPMed rs774482480, gnomAD rs774482480, REVEL 0.16, CADD 18.70
- M49V (p.Met49Val), TOPMed rs1450402163, gnomAD rs1450402163, REVEL 0.03, CADD 0.00
- L50R (p.Leu50Arg), rs747388089, gnomAD 3-46373050-CT-C, CADD 25.30
- L50L (p.Leu50Leu), gnomAD 3-46373050-C-T, CADD 6.71
- V51I (p.Val51Ile), gnomAD 3-46373053-G-A, REVEL 0.64, MetaLR 0.79
- I52T (p.Ile52Thr), cosmic curated COSV52751
- I52I (p.Ile52Ile), rs1701687138, gnomAD 3-46373058-C-A, CADD 5.90
- L53F (p.Leu53Phe), NCI-TCGA TCGA novel, Ensembl rs1701687187, Variant assessed as somatic; moderate impact.
- I54N (p.Ile54Asn), ExAC rs767459001, TOPMed rs767459001, gnomAD rs767459001, REVEL 0.16, CADD 22.40
- I54T (p.Ile54Thr), ExAC rs767459001, TOPMed rs767459001, gnomAD rs767459001, REVEL 0.06, CADD 12.70
- I54V (p.Ile54Val), TOPMed rs1701687270
- I54I (p.Ile54Ile), gnomAD 3-46373064-C-T, CADD 3.97
- L55P (p.Leu55Pro), 1000Genomes rs1799863, ESP rs1799863, ExAC rs1799863, TOPMed rs1799863
- L55Q (p.Leu55Gln), rs1799863, cosmic curated COSV99068, UniProt VAR 011840, 1000Genomes rs1799863, REVEL 0.43, CADD 24.30
- L55R (p.Leu55Arg), 1000Genomes rs1799863, ESP rs1799863, ExAC rs1799863, TOPMed rs1799863
- L55L (p.Leu55Leu), rs148106779, gnomAD 3-46373067-G-T, CADD 1.25
- I56K (p.Ile56Lys), TOPMed rs1459619557, gnomAD rs1459619557
- I56L (p.Ile56Leu), gnomAD rs1261999587, REVEL 0.06, CADD 3.31
- I56M (p.Ile56Met), TOPMed rs1701687677
- I56T (p.Ile56Thr), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, Variant assessed as somatic; moderate impact.
- N57I (p.Asn57Ile), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52750, Variant assessed as somatic; moderate impact.
- N57S (p.Asn57Ser), TOPMed rs1366408608
- N57T (p.Asn57Thr), TOPMed rs1366408608
- N57N (p.Asn57Asn), gnomAD 3-46373073-C-T, CADD 3.19
- C58W (p.Cys58Trp), gnomAD rs1211101172, REVEL 0.47, CADD 22.80
- C58* (p.Cys58Ter), gnomAD 3-46373076-C-A, CADD 34.00
- K59E (p.Lys59Glu), gnomAD 3-46373077-A-G, REVEL 0.28, MetaLR 0.20
- K59R (p.Lys59Arg), gnomAD 3-46373078-A-G, REVEL 0.11, MetaLR 0.13
- K59K (p.Lys59Lys), gnomAD 3-46373079-A-G, CADD 0.61
- R60K (p.Arg60Lys), cosmic curated COSV10511, gnomAD rs1300330603
- R60M (p.Arg60Met), gnomAD rs1300330603, REVEL 0.30, CADD 16.60
- R60S (p.Arg60Ser), rs1800940, ClinGen CA119362, cosmic curated COSV99433, ClinVar RCV000008673, REVEL 0.15, CADD 17.00, protective, Susceptibility to HIV infection
- R60G (p.Arg60Gly), gnomAD 3-46373076-CA-C, CADD 22.70
- L61L (p.Leu61Leu), gnomAD 3-46373085-G-A, CADD 0.66
- K62E (p.Lys62Glu), TOPMed rs1357139013, REVEL 0.17, CADD 22.70
- K62N (p.Lys62Asn), cosmic curated COSV52751
- K62R (p.Lys62Arg), UniProt VAR 003484, Uncertain significance, in UGCCR5-145B
- K62T (p.Lys62Thr), TOPMed rs917809042, gnomAD rs917809042, REVEL 0.08, CADD 14.50
- S63C (p.Ser63Cys), rs142829420, ClinGen CA2354580, ClinVar RCV001281053, ClinVar RCV003224551, REVEL 0.22, CADD 18.80, Uncertain significance, not provided; West Nile virus, susceptibility to; Type 1 diabetes mellitus 22
- S63N (p.Ser63Asn), gnomAD 3-46373090-G-A, REVEL 0.15, MetaLR 0.15
- S63S (p.Ser63Ser), rs1403636357, gnomAD 3-46373091-C-T, CADD 4.62
- M64I (p.Met64Ile), ExAC rs750002181, TOPMed rs750002181, gnomAD rs750002181, REVEL 0.30, CADD 22.50
- M64T (p.Met64Thr), TOPMed rs1701688268
- M64L (p.Met64Leu), gnomAD 3-46373092-A-T, REVEL 0.07, MetaLR 0.08
- M64V (p.Met64Val), gnomAD 3-46373092-A-G, REVEL 0.06, MetaLR 0.06
- T65I (p.Thr65Ile), Ensembl rs529010218
- D66G (p.Asp66Gly), NCI-TCGA Cosmic COSV5275, cosmic curated COSV52751, REVEL 0.66, CADD 25.00, Variant assessed as somatic; moderate impact.
- D66Y (p.Asp66Tyr), cosmic curated COSV52752
- D66V (p.Asp66Val), gnomAD 3-46373099-A-T, REVEL 0.64, MetaLR 0.37
- I67T (p.Ile67Thr), 1000Genomes rs199722561, REVEL 0.69, CADD 24.90
- I67I (p.Ile67Ile), gnomAD 3-46373103-C-T, CADD 7.21
Public CCR5 analysis runs
- CCR5 analysis run — CCR5 (941 variants) — completed 2026-08-19