RPA1 (P27694) variants and mutations
RPA1 (also known as P27694) is a human protein-coding gene encoding a replication protein A 70 kDa DNA-binding subunit protein. It binds single-stranded DNA during replication, recombination, and repair, protecting exposed DNA and coordinating checkpoint and repair proteins. Rare pathogenic variants can cause telomere and genome-maintenance disorders, while somatic dysregulation contributes to replication-stress tolerance in cancer. This analysis covers 662 RPA1 variants and mutations. Of these, 9.2% have computational variant effect predictions. Disease context includes pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, non-small cell lung adenocarcinoma, and cancer. Example RPA1 variants include V2F, G3A, and G3C.
Variant analysis overview
- Gene: RPA1
- Protein: P27694
- UniProt accession: P27694
- Organism: Homo sapiens
- Variants analyzed: 662
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 660 unspecified-consequence records; 2 substitution
- Prediction scores: 61 variants have prediction scores (9% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, non-small cell lung adenocarcinoma, cancer, basal cell carcinoma, prostate carcinoma, melanocytic nevus, lung cancer, melanoma, skin cancer, bronchus cancer, bronchial neoplasm, cutaneous melanoma.
Protein structure and variant hotspots
- Protein features: 7 post-translational modification sites.
- PTM context: 2 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 RPA1 variants
Examples include V2F, G3A, G3C, G3D, G3S, Q4H, Q4K, S6G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- V2F (p.Val2Phe), ExAC rs777883793
- G3A (p.Gly3Ala), TOPMed rs986142679, gnomAD rs986142679, Uncertain significance, not specified
- G3C (p.Gly3Cys), gnomAD rs952968242
- G3D (p.Gly3Asp), TOPMed rs986142679, gnomAD rs986142679
- G3S (p.Gly3Ser), gnomAD rs952968242
- Q4H (p.Gln4His), 1000Genomes rs5030749, ESP rs5030749, ExAC rs5030749, TOPMed rs5030749, Benign
- Q4K (p.Gln4Lys), gnomAD rs1395406468
- S6G (p.Ser6Gly), TOPMed rs1440763987, gnomAD rs1440763987
- S6I (p.Ser6Ile), gnomAD rs1301910097
- S6R (p.Ser6Arg), ExAC rs774560145, TOPMed rs774560145, gnomAD rs774560145
- E7* (p.Glu7Ter), gnomAD rs1234103628
- E7D (p.Glu7Asp), gnomAD rs1250958096
- G8R (p.Gly8Arg), ExAC rs759600887, gnomAD rs759600887
- A9D (p.Ala9Asp), gnomAD rs965554082
- A9S (p.Ala9Ser), TOPMed rs1163887393, gnomAD rs1163887393
- A9T (p.Ala9Thr), TOPMed rs1163887393, gnomAD rs1163887393
- A9V (p.Ala9Val), gnomAD rs965554082
- I10N (p.Ile10Asn), TOPMed rs1381711488, gnomAD rs1381711488
- I10T (p.Ile10Thr), TOPMed rs1381711488, gnomAD rs1381711488
- I10V (p.Ile10Val), TOPMed rs1420099438
- A11T (p.Ala11Thr), ExAC rs775945784, gnomAD rs775945784
- A12T (p.Ala12Thr), TOPMed rs1912106882
- M14I (p.Met14Ile), TOPMed rs1597421107
- M14V (p.Met14Val), gnomAD rs1423944457
- G17A (p.Gly17Ala), rs1912108371, ClinGen CA397577140, ClinVar RCV004449708, TOPMed rs1912108371, AlphaMissense 0.14, MetaLR 0.11, Uncertain significance, not specified
- G17R (p.Gly17Arg), 1000Genomes rs556447200, ExAC rs556447200, gnomAD rs556447200
- D18G (p.Asp18Gly), TOPMed rs1377749270
- D18N (p.Asp18Asn), TOPMed rs960070191
- D18V (p.Asp18Val), TOPMed rs1377749270
- D18Y (p.Asp18Tyr), TOPMed rs960070191
- T19A (p.Thr19Ala), Ensembl rs1912108998
- N20D (p.Asn20Asp), TOPMed rs1912109145
- N20T (p.Asn20Thr), Ensembl rs2151270651
- I21M (p.Ile21Met), TOPMed rs1302792384
- P23A (p.Pro23Ala), TOPMed rs1448087108, gnomAD rs1448087108
- P23S (p.Pro23Ser), TOPMed rs1448087108, gnomAD rs1448087108
- I24L (p.Ile24Leu), TOPMed rs1397149208, gnomAD rs1397149208
- L25H (p.Leu25His), gnomAD rs1458831946
- V27I (p.Val27Ile), ExAC rs769039530, gnomAD rs769039530
- I28T (p.Ile28Thr), ExAC rs777110403, TOPMed rs777110403, gnomAD rs777110403
- R31C (p.Arg31Cys), ExAC rs767278367, gnomAD rs767278367
- R31H (p.Arg31His), rs1238804059, NCI-TCGA Cosmic COSV5461, NCI-TCGA Cosmic COSV9962, TOPMed rs1238804059, AlphaMissense 0.95, MetaLR 0.37, Variant assessed as somatic; moderate impact.
- P32A (p.Pro32Ala), gnomAD rs1912156866
- P32L (p.Pro32Leu), NCI-TCGA Cosmic COSV5461, Variant assessed as somatic; moderate impact.
- I33V (p.Ile33Val), TOPMed rs1912157178, REVEL 0.11, CADD 22.00
- T35M (p.Thr35Met), TOPMed rs1286058622, gnomAD rs1286058622
- N37S (p.Asn37Ser), ExAC rs775200783, gnomAD rs775200783
- S38G (p.Ser38Gly), gnomAD rs1208250273
- S38T (p.Ser38Thr), ExAC rs760084921, gnomAD rs760084921
- P39L (p.Pro39Leu), ExAC rs764134040, TOPMed rs764134040, gnomAD rs764134040
- P40L (p.Pro40Leu), rs757098924, NCI-TCGA Cosmic COSV5461, ExAC rs757098924, TOPMed rs757098924, AlphaMissense 0.27, MetaLR 0.11, Variant assessed as somatic; moderate impact.
- P40Q (p.Pro40Gln), ExAC rs757098924, TOPMed rs757098924, gnomAD rs757098924
- R41H (p.Arg41His), rs758675207, ExAC rs758675207, TOPMed rs758675207, gnomAD rs758675207, AlphaMissense 0.99, MetaLR 0.52, Variant assessed as somatic; moderate impact.
- R41L (p.Arg41Leu), ExAC rs758675207, TOPMed rs758675207, gnomAD rs758675207
- Y42F (p.Tyr42Phe), ExAC rs780226221, TOPMed rs780226221, gnomAD rs780226221
- R43Q (p.Arg43Gln), rs1360031402, gnomAD rs1360031402, AlphaMissense 0.99, MetaLR 0.51, Variant assessed as somatic; moderate impact.
- L45H (p.Leu45His), TOPMed rs1479941735
- L45P (p.Leu45Pro), TOPMed rs1479941735
- M46I (p.Met46Ile), gnomAD rs1370952686
- M46V (p.Met46Val), ExAC rs747150308, TOPMed rs747150308, gnomAD rs747150308
- G49A (p.Gly49Ala), gnomAD rs1309951856
- G49R (p.Gly49Arg), ESP rs372026366, TOPMed rs372026366, gnomAD rs372026366
- N51S (p.Asn51Ser), ExAC rs754968818
- T52A (p.Thr52Ala), ExAC rs781732764, TOPMed rs781732764, gnomAD rs781732764
- T52S (p.Thr52Ser), rs748543005, ClinGen CA8275814, ClinVar RCV004193681, ExAC rs748543005, AlphaMissense 0.34, MetaLR 0.08, Uncertain significance, not specified
- L53V (p.Leu53Val), ExAC rs778351700, gnomAD rs778351700
- S55=, NCI-TCGA Cosmic COSV9962, Variant assessed as somatic; low impact.
- M57I (p.Met57Ile), rs1912185922, Ensembl rs1912185922, ClinGen CA397579131, ClinVar RCV004449706, AlphaMissense 0.99, MetaLR 0.28, Uncertain significance, not specified
- M57T (p.Met57Thr), Ensembl rs2151271637, Uncertain significance, not specified
- L58F (p.Leu58Phe), ESP rs372704235, ExAC rs372704235, TOPMed rs372704235, gnomAD rs372704235
- A59V (p.Ala59Val), ExAC rs756745134, TOPMed rs756745134, gnomAD rs756745134
- Q61* (p.Gln61Ter), TOPMed rs903933604, gnomAD rs903933604
- N63H (p.Asn63His), ExAC rs749714506
- P64L (p.Pro64Leu), TOPMed rs1912186962
- P64T (p.Pro64Thr), gnomAD rs1224471154
- L65F (p.Leu65Phe), NCI-TCGA Cosmic COSV9962, Variant assessed as somatic; moderate impact.
- V66M (p.Val66Met), TOPMed rs1475154953, gnomAD rs1475154953
- E67D (p.Glu67Asp), TOPMed rs1912187611
- E68K (p.Glu68Lys), ExAC rs746586892, TOPMed rs746586892, gnomAD rs746586892
- E69K (p.Glu69Lys), ExAC rs768217681, gnomAD rs768217681
- Q70E (p.Gln70Glu), ExAC rs761361601, TOPMed rs761361601, gnomAD rs761361601, Uncertain significance, not specified
- L71F (p.Leu71Phe), TOPMed rs1178847448, gnomAD rs1178847448
- S72C (p.Ser72Cys), gnomAD rs1325469305
- S72F (p.Ser72Phe), gnomAD rs1325469305
- S72P (p.Ser72Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S72Y (p.Ser72Tyr), NCI-TCGA Cosmic COSV5460, Variant assessed as somatic; moderate impact.
- S73G (p.Ser73Gly), NCI-TCGA Cosmic COSV5460, Ensembl rs2151271680, Variant assessed as somatic; moderate impact.
- S73I (p.Ser73Ile), NCI-TCGA Cosmic COSV5460, Variant assessed as somatic; moderate impact.
- N74S (p.Asn74Ser), TOPMed rs1429458685, gnomAD rs1429458685
- C75G (p.Cys75Gly), TOPMed rs1597422824
- C75S (p.Cys75Ser), TOPMed rs1597422824
- C75W (p.Cys75Trp), TOPMed rs1292876355, gnomAD rs1292876355
- V76I (p.Val76Ile), Ensembl rs1912189638
- C77R (p.Cys77Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C77S (p.Cys77Ser), Ensembl rs1567803571
- C77Y (p.Cys77Tyr), NCI-TCGA Cosmic COSV9962, Variant assessed as somatic; moderate impact.
- Q78* (p.Gln78Ter), TOPMed rs1912190128, gnomAD rs1912190128
- H80N (p.His80Asn), ExAC rs766103262, TOPMed rs766103262, gnomAD rs766103262, REVEL 0.59, CADD 26.70
- H80R (p.His80Arg), ExAC rs759747102, gnomAD rs759747102
- H80Y (p.His80Tyr), ExAC rs766103262, TOPMed rs766103262, gnomAD rs766103262
- F82S (p.Phe82Ser), ExAC rs767769316, TOPMed rs767769316, gnomAD rs767769316
- I83V (p.Ile83Val), ExAC rs752773475, TOPMed rs752773475, gnomAD rs752773475
- V84M (p.Val84Met), Ensembl rs1912191033
- T86A (p.Thr86Ala), TOPMed rs1213809143, gnomAD rs1213809143
- L87V (p.Leu87Val), ExAC rs754348776, gnomAD rs754348776
- K88R (p.Lys88Arg), TOPMed rs1187542931, gnomAD rs1187542931
- G90R (p.Gly90Arg), rs1411457047, ClinGen CA397580034, ClinVar RCV004224483, TOPMed rs1411457047, AlphaMissense 0.83, MetaLR 0.35, Uncertain significance, not specified
- R91M (p.Arg91Met), Ensembl rs2151271721
- R92G (p.Arg92Gly), rs2543651528, ClinGen CA397581813, ClinVar RCV004130707, Uncertain significance, not specified
- R92T (p.Arg92Thr), NCI-TCGA Cosmic COSV5460, Variant assessed as somatic; moderate impact.
- V93I (p.Val93Ile), ExAC rs748785852, gnomAD rs748785852
- V93L (p.Val93Leu), NCI-TCGA Cosmic COSV9962, Variant assessed as somatic; moderate impact.
- V94I (p.Val94Ile), 1000Genomes rs553472326, ExAC rs553472326, gnomAD rs553472326
- E98D (p.Glu98Asp), 1000Genomes rs199998753, ExAC rs199998753, TOPMed rs199998753, gnomAD rs199998753
- E98G (p.Glu98Gly), ExAC rs745684143, TOPMed rs745684143, gnomAD rs745684143
- L102F (p.Leu102Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S104P (p.Ser104Pro), Ensembl rs1912560658
- A105G (p.Ala105Gly), rs775867881, ClinGen CA8275890, ClinVar RCV004231337, ClinVar RCV005926878, AlphaMissense 0.10, MetaLR 0.09, Uncertain significance, not specified
- E106K (p.Glu106Lys), TOPMed rs1057051634
- V108A (p.Val108Ala), TOPMed rs1457193252, gnomAD rs1457193252
- V108L (p.Val108Leu), ExAC rs200742050, gnomAD rs200742050
- G109R (p.Gly109Arg), gnomAD rs1912561641
- G109V (p.Gly109Val), ExAC rs776899154, TOPMed rs776899154, gnomAD rs776899154
- V110L (p.Val110Leu), ExAC rs761951170, TOPMed rs761951170, gnomAD rs761951170
- V110M (p.Val110Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K111N (p.Lys111Asn), NCI-TCGA TCGA novel, ExAC rs368130064, gnomAD rs368130064, Variant assessed as somatic; moderate impact.
- I112M (p.Ile112Met), rs750892999, ClinGen CA8275896, ClinVar RCV004117798, ExAC rs750892999, AlphaMissense 0.19, MetaLR 0.23, Uncertain significance, not specified
- I112S (p.Ile112Ser), gnomAD rs1912562389
- I112T (p.Ile112Thr), gnomAD rs1912562389
- N114D (p.Asn114Asp), TOPMed rs1912562701
- P115L (p.Pro115Leu), ESP rs371452640, ExAC rs371452640, TOPMed rs371452640, gnomAD rs371452640
- P115S (p.Pro115Ser), Ensembl rs1181652461, Uncertain significance, not specified
- V116L (p.Val116Leu), ExAC rs766696018, TOPMed rs766696018, gnomAD rs766696018, Uncertain significance, not specified
- P117S (p.Pro117Ser), gnomAD rs1405265362
- Y118C (p.Tyr118Cys), TOPMed rs1488143769, gnomAD rs1488143769
- Y118H (p.Tyr118His), ExAC rs751915350, gnomAD rs751915350
- N119D (p.Asn119Asp), gnomAD rs1401730606
- E120A (p.Glu120Ala), gnomAD rs1440835891
- E120G (p.Glu120Gly), gnomAD rs1440835891
- G121* (p.Gly121Ter), ExAC rs747566361, gnomAD rs747566361
- L122F (p.Leu122Phe), gnomAD rs1487064997
- G123R (p.Gly123Arg), ExAC rs768521178, TOPMed rs768521178, gnomAD rs768521178, Uncertain significance, not specified
- P125L (p.Pro125Leu), TOPMed rs905403945, gnomAD rs905403945
- P125T (p.Pro125Thr), ExAC rs781578904, gnomAD rs781578904
- A128P (p.Ala128Pro), TOPMed rs1358739794, gnomAD rs1358739794
- A128V (p.Ala128Val), TOPMed rs1384185104, gnomAD rs1384185104
- P129L (p.Pro129Leu), gnomAD rs1402030559
- P129T (p.Pro129Thr), TOPMed rs1913409068
- P130S (p.Pro130Ser), gnomAD rs1299089490
- A131V (p.Ala131Val), rs577689051, NCI-TCGA Cosmic COSV5461, 1000Genomes rs577689051, ExAC rs577689051, AlphaMissense 0.06, MetaLR 0.07, Variant assessed as somatic; moderate impact.
- A133T (p.Ala133Thr), gnomAD rs1310466852
- A134G (p.Ala134Gly), ExAC rs762917348, gnomAD rs762917348
- S135C (p.Ser135Cys), gnomAD rs1187304739, Uncertain significance, not specified
- P136L (p.Pro136Leu), Ensembl rs1913410805
- A137E (p.Ala137Glu), gnomAD rs1284635352
- A137T (p.Ala137Thr), NCI-TCGA Cosmic COSV5460, Variant assessed as somatic; moderate impact.
- A138T (p.Ala138Thr), NCI-TCGA Cosmic COSV5461, Variant assessed as somatic; moderate impact.
- A138V (p.Ala138Val), TOPMed rs1913411066, gnomAD rs1913411066, Uncertain significance, not specified
- S139N (p.Ser139Asn), ExAC rs774802762, gnomAD rs774802762
- S140R (p.Ser140Arg), gnomAD rs1286371250
- R141S (p.Arg141Ser), Ensembl rs1597445738
- P142L (p.Pro142Leu), TOPMed rs1913411876
- P142S (p.Pro142Ser), TOPMed rs1470071804
- P144L (p.Pro144Leu), TOPMed rs1037678691, gnomAD rs1037678691
- P144S (p.Pro144Ser), Ensembl rs1913412201
- Q145* (p.Gln145Ter), gnomAD rs1258709789
- N146K (p.Asn146Lys), rs2543675166, ClinGen CA397552905, ClinVar RCV004267773, Uncertain significance, not specified
- S148G (p.Ser148Gly), ExAC rs370337203, TOPMed rs370337203, gnomAD rs370337203, Uncertain significance, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6
- S149L (p.Ser149Leu), ExAC rs753437800, TOPMed rs753437800, gnomAD rs753437800
- G150E (p.Gly150Glu), ExAC rs764785914, TOPMed rs764785914, gnomAD rs764785914
- G150V (p.Gly150Val), ExAC rs764785914, TOPMed rs764785914, gnomAD rs764785914
- M151V (p.Met151Val), Ensembl rs2151283998
- G152V (p.Gly152Val), gnomAD rs1230507918
- T154A (p.Thr154Ala), ESP rs145953310, ExAC rs145953310, TOPMed rs145953310, gnomAD rs145953310
- T154N (p.Thr154Asn), ExAC rs755020262, TOPMed rs755020262, gnomAD rs755020262
- T154P (p.Thr154Pro), ESP rs145953310, ExAC rs145953310, TOPMed rs145953310, gnomAD rs145953310
- V155A (p.Val155Ala), ExAC rs752573944, gnomAD rs752573944
- V155G (p.Val155Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V155L (p.Val155Leu), Ensembl rs888680530
- S156A (p.Ser156Ala), Ensembl rs1007090785
Public RPA1 analysis runs
- RPA1 analysis run — RPA1 (662 variants) — completed 2026-08-22