PARP1 (Poly [ADP-ribose] polymerase 1) variants and mutations
PARP1 (also known as Poly [ADP-ribose] polymerase 1) is a human protein-coding gene encoding a poly [ADP-ribose] polymerase 1 protein. It detects DNA strand breaks and adds poly(ADP-ribose) chains to itself and other proteins, recruiting repair machinery and coordinating stress responses. Tumors deficient in homologous recombination can become highly dependent on this pathway, creating the synthetic-lethal basis for PARP-inhibitor therapy. This analysis covers 1,804 PARP1 variants and mutations. Of these, 55% have computational variant effect predictions. Example PARP1 variants include A2G, A2V, and E3G.
Variant analysis overview
- Gene: PARP1
- Protein: Poly [ADP-ribose] polymerase 1
- UniProt accession: P09874
- Organism: Homo sapiens
- Variants analyzed: 1804
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,627 unspecified-consequence records; 1 stop retained variant; 65 missense variants; 79 synonymous variants; 14 frameshift variants; 1 in-frame deletions; 7 stop-gained variants; 6 splice-region variants; 1 in-frame insertions; 4 substitution
- Prediction scores: 999 variants have prediction scores (55% of the analyzed set).
Protein structure and variant hotspots
- Protein features: 5 domains; 16 binding sites; 38 post-translational modification sites.
- Structural context: 1,205 variants have structural context.
- PTM context: 72 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, MaveDB, LitVar.
Notable PARP1 variants
Examples include A2G, A2V, E3G, S4C, S4F, S4P, S4Y, S5L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2G (p.Ala2Gly), cosmic curated COSV64687, ExAC rs769133844, TOPMed rs769133844, gnomAD rs769133844
- A2V (p.Ala2Val), cosmic curated COSV64687, ExAC rs769133844, TOPMed rs769133844, gnomAD rs769133844, REVEL 0.21, CADD 24.20
- E3G (p.Glu3Gly), Ensembl rs2102750353
- S4C (p.Ser4Cys), TOPMed rs1347824092, gnomAD rs1347824092
- S4F (p.Ser4Phe), TOPMed rs1347824092, gnomAD rs1347824092, REVEL 0.07, CADD 23.30
- S4P (p.Ser4Pro), TOPMed rs1339302801, gnomAD rs1339302801, REVEL 0.02, CADD 18.20
- S4Y (p.Ser4Tyr), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10082, Variant assessed as somatic; moderate impact.
- S5L (p.Ser5Leu), 1000Genomes rs201256399, ExAC rs201256399, TOPMed rs201256399, gnomAD rs201256399, REVEL 0.07, CADD 22.30, Likely benign
- S5T (p.Ser5Thr), Ensembl rs2102750346
- S5W (p.Ser5Trp), rs201256399, ClinGen CA1423351, ClinVar RCV003904350, 1000Genomes rs201256399, REVEL 0.10, CADD 24.00, Likely benign, PARP1-related disorder
- K7R (p.Lys7Arg), TOPMed rs1665185383
- K7T (p.Lys7Thr), TOPMed rs1665185383
- L8F (p.Leu8Phe), gnomAD rs1341567065, REVEL 0.11, CADD 24.80
- Y9C (p.Tyr9Cys), cosmic curated COSV64687, ExAC rs770635699, TOPMed rs770635699, gnomAD rs770635699, REVEL 0.41, CADD 31.00
- R10G (p.Arg10Gly), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10082, REVEL 0.12, CADD 24.50, Variant assessed as somatic; moderate impact.
- R10P (p.Arg10Pro), ExAC rs746792662, TOPMed rs746792662, gnomAD rs746792662, REVEL 0.21, CADD 28.80
- R10Q (p.Arg10Gln), ExAC rs746792662, TOPMed rs746792662, gnomAD rs746792662, REVEL 0.05, CADD 23.30
- V11I (p.Val11Ile), TOPMed rs1488383078, gnomAD rs1488383078, REVEL 0.10, CADD 24.10
- E12D (p.Glu12Asp), cosmic curated COSV10528, 1000Genomes rs777484474, ExAC rs777484474, REVEL 0.24, CADD 24.40
- E12G (p.Glu12Gly), NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, Variant assessed as somatic; moderate impact.
- A14G (p.Ala14Gly), Ensembl rs2102750321
- A14T (p.Ala14Thr), Ensembl rs2102750324
- K15R (p.Lys15Arg), gnomAD rs1334838918, REVEL 0.30, CADD 29.40
- S16G (p.Ser16Gly), TOPMed rs1336568282, gnomAD rs1336568282, REVEL 0.43, CADD 32.00
- S16N (p.Ser16Asn), Ensembl rs2102750316, Uncertain significance, not specified
- S16T (p.Ser16Thr), Ensembl rs2102750316
- G17R (p.Gly17Arg), ExAC rs771934563, gnomAD rs771934563, REVEL 0.56, CADD 29.50
- R18C (p.Arg18Cys), TOPMed rs1432106341, gnomAD rs1432106341
- R18G (p.Arg18Gly), TOPMed rs1432106341, gnomAD rs1432106341, REVEL 0.66, CADD 32.00
- A19S (p.Ala19Ser), ExAC rs747988833, gnomAD rs747988833, REVEL 0.14, CADD 23.60
- A19T (p.Ala19Thr), ExAC rs747988833, gnomAD rs747988833
- S20A (p.Ser20Ala), TOPMed rs1665184611
- S20F (p.Ser20Phe), ExAC rs778958457, gnomAD rs778958457, REVEL 0.35, CADD 32.00
- C21F (p.Cys21Phe), gnomAD rs1665184470
- C21Y (p.Cys21Tyr), gnomAD rs1665184470, REVEL 0.92, CADD 29.80
- K22E (p.Lys22Glu), ExAC rs754981299, gnomAD rs754981299, REVEL 0.40, CADD 32.00
- K23N (p.Lys23Asn), gnomAD rs1185554480, REVEL 0.12, CADD 23.50
- K23T (p.Lys23Thr), gnomAD rs1416842124, REVEL 0.22, CADD 24.70
- C24R (p.Cys24Arg), Ensembl rs1665184321, REVEL 0.82, CADD 32.00
- S25N (p.Ser25Asn), gnomAD rs1665184257, REVEL 0.03, CADD 23.30
- E26D (p.Glu26Asp), gnomAD rs1237764785
- E26K (p.Glu26Lys), NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, REVEL 0.11, CADD 23.40, Variant assessed as somatic; moderate impact.
- E26V (p.Glu26Val), Ensembl rs1665184138
- S27C (p.Ser27Cys), Ensembl rs2102750287
- S27I (p.Ser27Ile), ExAC rs754042347, gnomAD rs754042347, REVEL 0.08, CADD 23.10
- S27R (p.Ser27Arg), ExAC rs780414059, gnomAD rs780414059, REVEL 0.10, CADD 23.00
- S27T (p.Ser27Thr), ExAC rs754042347, gnomAD rs754042347, REVEL 0.04, CADD 21.90
- I28M (p.Ile28Met), Ensembl rs2102750280
- I28V (p.Ile28Val), Ensembl rs1665183958
- K30R (p.Lys30Arg), Ensembl rs1665183865, REVEL 0.35, CADD 32.00
- D31A (p.Asp31Ala), gnomAD rs1665183726
- D31H (p.Asp31His), ExAC rs756350417, TOPMed rs756350417, gnomAD rs756350417, REVEL 0.47, CADD 31.00
- D31N (p.Asp31Asn), cosmic curated COSV64687, ExAC rs756350417, TOPMed rs756350417, gnomAD rs756350417, REVEL 0.15, CADD 25.60
- D31V (p.Asp31Val), gnomAD rs1665183726
- S32L (p.Ser32Leu), ExAC rs750681422, TOPMed rs750681422, gnomAD rs750681422, REVEL 0.42, CADD 32.00, Uncertain significance, not specified
- S32W (p.Ser32Trp), ExAC rs750681422, TOPMed rs750681422, gnomAD rs750681422, REVEL 0.65, CADD 32.00, Uncertain significance
- L33F (p.Leu33Phe), rs767731025, ClinGen CA1423338, ClinVar RCV004290049, ExAC rs767731025, REVEL 0.31, CADD 28.60, Uncertain significance, not specified
- R34G (p.Arg34Gly), Ensembl rs2102750262, REVEL 0.73, CADD 31.00
- R34L (p.Arg34Leu), ExAC rs762258231, gnomAD rs762258231
- R34Q (p.Arg34Gln), ExAC rs762258231, gnomAD rs762258231, REVEL 0.82, CADD 32.00
- M35I (p.Met35Ile), TOPMed rs912149989, REVEL 0.12, CADD 23.10
- M35L (p.Met35Leu), ExAC rs751984430, gnomAD rs751984430
- M35V (p.Met35Val), ExAC rs751984430, gnomAD rs751984430, REVEL 0.14, CADD 24.80, Uncertain significance, not specified
- A36V (p.Ala36Val), Ensembl rs2102750253
- I37F (p.Ile37Phe), TOPMed rs1285064497, gnomAD rs1285064497, REVEL 0.06, CADD 24.40
- I37V (p.Ile37Val), TOPMed rs1285064497, gnomAD rs1285064497, REVEL 0.04, CADD 21.00
- M38I (p.Met38Ile), ExAC rs764699034, TOPMed rs764699034, gnomAD rs764699034, REVEL 0.22, CADD 23.10
- V39L (p.Val39Leu), ESP rs142025196, ExAC rs142025196, TOPMed rs142025196, gnomAD rs142025196, REVEL 0.23, CADD 24.80
- V39M (p.Val39Met), cosmic curated COSV64687, ESP rs142025196, ExAC rs142025196, TOPMed rs142025196, REVEL 0.31, CADD 29.10
- Q40R (p.Gln40Arg), Ensembl rs2102750242
- S41* (p.Ser41Ter), ExAC rs768342881, gnomAD rs768342881
- S41L (p.Ser41Leu), rs768342881, NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, ExAC rs768342881, REVEL 0.62, CADD 33.00, Variant assessed as somatic; moderate impact.
- S41P (p.Ser41Pro), Ensembl rs2102747301
- S41T (p.Ser41Thr), Ensembl rs2102747301
- P42H (p.Pro42His), Ensembl rs2102747290
- M43L (p.Met43Leu), TOPMed rs1220828656, gnomAD rs1220828656, REVEL 0.15, CADD 18.30
- M43T (p.Met43Thr), 1000Genomes rs202022212, ExAC rs202022212, TOPMed rs202022212, gnomAD rs202022212, REVEL 0.42, CADD 22.60
- M43V (p.Met43Val), TOPMed rs1220828656, gnomAD rs1220828656, REVEL 0.15, CADD 16.90
- D45H (p.Asp45His), TOPMed rs946978561, gnomAD rs946978561, REVEL 0.64, CADD 27.80
- G46A (p.Gly46Ala), Ensembl rs2102747283
- K47E (p.Lys47Glu), TOPMed rs1360722722, gnomAD rs1360722722, REVEL 0.38, CADD 29.30
- K47N (p.Lys47Asn), Ensembl rs2102747279
- V48S (p.Val48Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P49S (p.Pro49Ser), Ensembl rs2102747273
- P49T (p.Pro49Thr), Ensembl rs2102747273
- H50L (p.His50Leu), TOPMed rs1397984634, gnomAD rs1397984634
- H50Q (p.His50Gln), cosmic curated COSV10652, gnomAD rs1665054322, REVEL 0.14, CADD 22.90
- H50R (p.His50Arg), TOPMed rs1397984634, gnomAD rs1397984634, REVEL 0.15, CADD 22.50
- W51* (p.Trp51Ter), Ensembl rs2102747264, CADD 38.00
- W51C (p.Trp51Cys), Ensembl rs2102747264
- Y52N (p.Tyr52Asn), Ensembl rs2102747262
- H53L (p.His53Leu), Ensembl rs2102747256
- H53Q (p.His53Gln), rs375440192, ClinGen CA345046345, ClinVar RCV004110356, ESP rs375440192, REVEL 0.90, CADD 24.30, Uncertain significance, not specified
- F54L (p.Phe54Leu), rs3738708, UniProt VAR 050460, TOPMed rs3738708, gnomAD rs3738708, REVEL 0.06, CADD 21.80
- S55F (p.Ser55Phe), cosmic curated COSV10528, ExAC rs757556995, gnomAD rs757556995, REVEL 0.41, CADD 28.40
- S55T (p.Ser55Thr), ExAC rs781263314, REVEL 0.03, CADD 18.50
- S55Y (p.Ser55Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C56F (p.Cys56Phe), Ensembl rs2102747242
- C56Y (p.Cys56Tyr), Ensembl rs2102747242
- F57L (p.Phe57Leu), Ensembl rs1262677082, REVEL 0.63, CADD 29.80
- W58C (p.Trp58Cys), Ensembl rs2102747230
- W58L (p.Trp58Leu), NCI-TCGA TCGA novel, Ensembl rs2102747232, Variant assessed as somatic; moderate impact.
- W58R (p.Trp58Arg), cosmic curated COSV10747, ESP rs370621373, ExAC rs370621373, TOPMed rs370621373, REVEL 0.72, CADD 31.00
- W58S (p.Trp58Ser), Ensembl rs2102747232
- K59E (p.Lys59Glu), gnomAD rs1426571960, REVEL 0.09, CADD 23.50
- K59R (p.Lys59Arg), gnomAD rs1665053768, REVEL 0.14, CADD 23.20
- V60M (p.Val60Met), ExAC rs778130497, gnomAD rs778130497, REVEL 0.04, CADD 19.90
- G61C (p.Gly61Cys), Ensembl rs2102747224
- G61D (p.Gly61Asp), ExAC rs758791748, TOPMed rs758791748, gnomAD rs758791748, REVEL 0.15, CADD 22.60
- G61S (p.Gly61Ser), Ensembl rs2102747224, REVEL 0.13, CADD 23.00
- G61V (p.Gly61Val), ExAC rs758791748, TOPMed rs758791748, gnomAD rs758791748, REVEL 0.11, CADD 22.40, Uncertain significance, not specified
- H62Q (p.His62Gln), ExAC rs755617552, TOPMed rs755617552, gnomAD rs755617552, REVEL 0.02, CADD 16.50, Uncertain significance, not specified
- H62R (p.His62Arg), ExAC rs753181414, gnomAD rs753181414, REVEL 0.07, CADD 16.20
- S63F (p.Ser63Phe), cosmic curated COSV10468, TOPMed rs1422347543, gnomAD rs1422347543, REVEL 0.07, CADD 22.30
- I64M (p.Ile64Met), Ensembl rs2102747211
- I64S (p.Ile64Ser), ExAC rs766952486, gnomAD rs766952486, REVEL 0.10, CADD 21.90
- I64V (p.Ile64Val), ExAC rs750007700, gnomAD rs750007700
- R65L (p.Arg65Leu), ExAC rs773909453, gnomAD rs773909453
- R65P (p.Arg65Pro), ExAC rs773909453, gnomAD rs773909453
- R65Q (p.Arg65Gln), cosmic curated COSV10082, ExAC rs773909453, gnomAD rs773909453, REVEL 0.03, CADD 18.30
- R65W (p.Arg65Trp), cosmic curated COSV10468, 1000Genomes rs377491451, ESP rs377491451, ExAC rs377491451, REVEL 0.08, CADD 22.90
- H66Y (p.His66Tyr), Ensembl rs2102747200
- P67H (p.Pro67His), Ensembl rs2102747191
- P67L (p.Pro67Leu), Ensembl rs2102747191
- P67S (p.Pro67Ser), Ensembl rs2102747194
- D68N (p.Asp68Asn), Ensembl rs2102747186
- D68V (p.Asp68Val), Ensembl rs2102747184
- V69F (p.Val69Phe), ExAC rs762887304, TOPMed rs762887304, gnomAD rs762887304
- V69I (p.Val69Ile), ExAC rs762887304, TOPMed rs762887304, gnomAD rs762887304, REVEL 0.06, CADD 0.02
- V71L (p.Val71Leu), Ensembl rs2102747174
- V71M (p.Val71Met), Ensembl rs2102747174
- D72A (p.Asp72Ala), ESP rs147105590, ExAC rs147105590, TOPMed rs147105590, gnomAD rs147105590, REVEL 0.10, CADD 22.70
- D72G (p.Asp72Gly), ESP rs147105590, ExAC rs147105590, TOPMed rs147105590, gnomAD rs147105590, REVEL 0.11, CADD 23.10
- D72Y (p.Asp72Tyr), Ensembl rs2102747171
- G73E (p.Gly73Glu), Ensembl rs2102747162, REVEL 0.79, CADD 23.70
- G73V (p.Gly73Val), Ensembl rs2102747162, REVEL 0.80, CADD 24.90
- G73W (p.Gly73Trp), Ensembl rs2102747168
- F74L (p.Phe74Leu), rs759516960, NCI-TCGA Cosmic COSV1008, cosmic curated COSV10082, ExAC rs759516960, REVEL 0.23, CADD 23.70, Variant assessed as somatic; moderate impact.
- S75C (p.Ser75Cys), Ensembl rs2102747157
- S75P (p.Ser75Pro), 1000Genomes rs182219056, ExAC rs182219056, TOPMed rs182219056, gnomAD rs182219056, REVEL 0.06, CADD 22.70
- R78G (p.Arg78Gly), ExAC rs770918209, gnomAD rs770918209
- R78L (p.Arg78Leu), cosmic curated COSV10082, ESP rs139202063, ExAC rs139202063, gnomAD rs139202063
- R78Q (p.Arg78Gln), cosmic curated COSV64687, ESP rs139202063, ExAC rs139202063, gnomAD rs139202063, REVEL 0.44, CADD 26.90
- R78W (p.Arg78Trp), rs770918209, NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, ExAC rs770918209, REVEL 0.58, CADD 27.90, Variant assessed as somatic; moderate impact.
- W79L (p.Trp79Leu), NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, Variant assessed as somatic; moderate impact.
- W79R (p.Trp79Arg), Ensembl rs2102747144
- D80Y (p.Asp80Tyr), Ensembl rs2102747142, REVEL 0.37, CADD 27.20
- D81E (p.Asp81Glu), 1000Genomes rs1805404, ESP rs1805404, ExAC rs1805404, TOPMed rs1805404, REVEL 0.59, CADD 25.30
- D81G (p.Asp81Gly), NCI-TCGA Cosmic COSV6468, cosmic curated COSV64687, Variant assessed as somatic; moderate impact.
- D81N (p.Asp81Asn), ExAC rs777908389, gnomAD rs777908389, REVEL 0.55, CADD 27.60
- Q82E (p.Gln82Glu), TOPMed rs1222634275, gnomAD rs1222634275, REVEL 0.58, CADD 26.20
- Q83* (p.Gln83Ter), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10082, Ensembl rs2102747134, Variant assessed as somatic; high impact.
- Q83R (p.Gln83Arg), ExAC rs748579213, TOPMed rs748579213, gnomAD rs748579213, REVEL 0.14, CADD 24.20
- K84E (p.Lys84Glu), ExAC rs779380683, gnomAD rs779380683
- V85F (p.Val85Phe), gnomAD rs1254416670
- V85I (p.Val85Ile), gnomAD rs1254416670, REVEL 0.02, CADD 12.60
- K86R (p.Lys86Arg), ESP rs373081722, ExAC rs373081722, TOPMed rs373081722, gnomAD rs373081722, REVEL 0.21, CADD 23.30
- T88I (p.Thr88Ile), Ensembl rs2102747125
- A89T (p.Ala89Thr), TOPMed rs1024721663, gnomAD rs1024721663, REVEL 0.05, CADD 21.50
- A89V (p.Ala89Val), cosmic curated COSV10747, Ensembl rs1558243852, REVEL 0.10, CADD 20.90
- E90K (p.Glu90Lys), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10082, Variant assessed as somatic; moderate impact.
- A91G (p.Ala91Gly), Ensembl rs2102747116
- A91V (p.Ala91Val), Ensembl rs2102747116, REVEL 0.04, CADD 22.20
- G92R (p.Gly92Arg), ExAC rs762832683, gnomAD rs762832683
- G93V (p.Gly93Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V94A (p.Val94Ala), TOPMed rs1199388635, REVEL 0.02, CADD 13.20
- V94M (p.Val94Met), Ensembl rs2102747105, REVEL 0.01, CADD 13.80
- T95=, NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; low impact.
- T95A (p.Thr95Ala), ExAC rs752593326, TOPMed rs752593326, gnomAD rs752593326
- G96S (p.Gly96Ser), Ensembl rs2102747102, REVEL 0.12, CADD 26.00
- G98S (p.Gly98Ser), TOPMed rs1558241049, gnomAD rs1558241049, REVEL 0.11, CADD 18.70
- Q99H (p.Gln99His), Ensembl rs1664835801
- D100E (p.Asp100Glu), TOPMed rs1194997553, gnomAD rs1194997553, REVEL 0.04, CADD 2.18
- D100G (p.Asp100Gly), Ensembl rs1664835464, REVEL 0.06, CADD 10.50
- D100N (p.Asp100Asn), TOPMed rs1447523073, gnomAD rs1447523073, REVEL 0.05, CADD 12.60
- I102V (p.Ile102Val), Ensembl rs1558241042, REVEL 0.03, CADD 0.55
- S104I (p.Ser104Ile), ExAC rs760027246
- S104R (p.Ser104Arg), NCI-TCGA Cosmic COSV6468, Variant assessed as somatic; moderate impact.
- K105E (p.Lys105Glu), rs1289654275, TOPMed rs1289654275, gnomAD rs1289654275, REVEL 0.17, CADD 17.90, Variant assessed as somatic; moderate impact.
- A106T (p.Ala106Thr), ExAC rs771624359, gnomAD rs771624359, REVEL 0.02, CADD 0.06
Public PARP1 analysis runs
- PARP1 analysis run — PARP1 (1,804 variants) — completed 2026-08-22