ERBB2 (P04626) variants and mutations
ERBB2 (also known as P04626) is a human protein-coding gene encoding a receptor tyrosine-protein kinase erbB-2 protein. ERBB2, also called HER2, is a cell-surface receptor tyrosine kinase that works with other ERBB receptors to transmit growth signals. It helps organize signaling and cytoskeletal responses, and abnormal ERBB2 activity is a major feature of several cancers. This analysis covers 5,694 ERBB2 variants and mutations. Of these, 27% have computational variant effect predictions. Disease context includes non-small cell lung carcinoma, cancer, and gastric cancer. Example ERBB2 variants include E2*, E2G, and E2K.
Variant analysis overview
- Gene: ERBB2
- Protein: P04626
- UniProt accession: P04626
- Organism: Homo sapiens
- Variants analyzed: 5694
- Variant scope: all variants
- Completed: 2026-07-24
Variant and mutation evidence
- Variant composition: 5,569 unspecified-consequence records; 53 synonymous variants; 12 frameshift variants; 50 missense variants; 5 stop-gained variants; 2 splice-region variants; 2 substitution
- Prediction scores: 1,532 variants have prediction scores (27% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: non-small cell lung carcinoma, cancer, gastric cancer, breast carcinoma, gastric adenocarcinoma, neoplasm, urinary bladder cancer, lung adenocarcinoma, breast cancer, HER2 positive breast carcinoma, breast neoplasm, urinary bladder carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 2 binding sites; 19 post-translational modification sites.
- Structural context: 1,299 variants have structural context.
- PTM context: 99 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 ERBB2 variants
Examples include E2*, E2G, E2K, E2Q, E2V, E2E, E2D, L3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2* (p.Glu2Ter), Ensembl rs2145266957, CADD 37.00
- E2G (p.Glu2Gly), Ensembl rs1379316719, REVEL 0.37, CADD 26.30
- E2K (p.Glu2Lys), Ensembl rs2145266957, REVEL 0.28, CADD 22.80
- E2Q (p.Glu2Gln), Ensembl rs2145266957
- E2V (p.Glu2Val), Ensembl rs1379316719, REVEL 0.41, CADD 25.10
- E2E (p.Glu2Glu), gnomAD 17-39700244-G-A, CADD 13.90
- E2D (p.Glu2Asp), gnomAD 17-39700244-G-T, REVEL 0.15, CADD 21.40
- L3V (p.Leu3Val), rs2058005545, ClinGen CA399266410, ClinVar RCV001917179, Ensembl rs2058005545, AlphaMissense 0.08, MetaLR 0.52, Uncertain significance, not provided
- L3M (p.Leu3Met), gnomAD 17-39700245-C-A, REVEL 0.35, CADD 22.60
- L3L (p.Leu3Leu), rs2058005545, gnomAD 17-39700245-C-T, AlphaMissense 0.08, MetaLR 0.52
- L3P (p.Leu3Pro), gnomAD 17-39700246-T-C, REVEL 0.57, CADD 28.50
- A4G (p.Ala4Gly), TOPMed rs1428243929, gnomAD rs1428243929, REVEL 0.13, CADD 24.30
- A4P (p.Ala4Pro), TOPMed rs1039589946, gnomAD rs1039589946, Uncertain significance
- A4S (p.Ala4Ser), rs1039589946, ClinGen CA290420195, ClinVar RCV004380477, TOPMed rs1039589946, REVEL 0.15, CADD 22.30, Uncertain significance, not specified
- A4T (p.Ala4Thr), TOPMed rs1039589946, gnomAD rs1039589946, REVEL 0.22, CADD 22.80, Uncertain significance
- A4V (p.Ala4Val), TOPMed rs1428243929, gnomAD rs1428243929, REVEL 0.23, CADD 23.50
- A4R (p.Ala4Arg), gnomAD 17-39700246-TG-T, CADD 29.20
- A4E (p.Ala4Glu), gnomAD 17-39700249-C-A, REVEL 0.31, CADD 22.10
- A4A (p.Ala4Ala), rs2145267350, gnomAD 17-39700250-G-T, CADD 15.10
- A5D (p.Ala5Asp), Ensembl rs2145267458, REVEL 0.54, CADD 22.70
- A5G (p.Ala5Gly), Ensembl rs2145267458
- A5P (p.Ala5Pro), Ensembl rs2145267398
- A5T (p.Ala5Thr), Ensembl rs2145267398, REVEL 0.33, CADD 22.80
- A5V (p.Ala5Val), Ensembl rs2145267458, REVEL 0.28, CADD 22.80
- A5S (p.Ala5Ser), gnomAD 17-39700251-G-T, REVEL 0.31, CADD 22.30
- A5A (p.Ala5Ala), rs1160835488, gnomAD 17-39700253-C-A, CADD 15.00
- L6S (p.Leu6Ser), Ensembl rs2145267660, REVEL 0.28, CADD 23.10
- L6M (p.Leu6Met), gnomAD 17-39700254-T-A, REVEL 0.15, CADD 22.70
- L6L (p.Leu6Leu), rs1206670744, gnomAD 17-39700254-T-C, CADD 15.30
- L6V (p.Leu6Val), gnomAD 17-39700254-T-G, REVEL 0.14, CADD 22.40
- L6W (p.Leu6Trp), gnomAD 17-39700255-T-G, REVEL 0.16, CADD 21.00
- L6F (p.Leu6Phe), gnomAD 17-39700255-TG-T, CADD 25.30
- L6* (p.Leu6Ter), gnomAD 17-39700255-T-A, CADD 36.00
- C7G (p.Cys7Gly), Ensembl rs2145267694
- C7S (p.Cys7Ser), Ensembl rs2145267694, REVEL 0.21, CADD 16.90
- C7Y (p.Cys7Tyr), Ensembl rs2145267746, REVEL 0.19, CADD 13.90
- C7R (p.Cys7Arg), gnomAD 17-39700257-T-C, REVEL 0.34, CADD 22.60
- C7F (p.Cys7Phe), gnomAD 17-39700258-G-T, REVEL 0.25, CADD 14.90
- C7* (p.Cys7Ter), gnomAD 17-39700259-C-A, CADD 35.00
- C7C (p.Cys7Cys), rs2058006564, gnomAD 17-39700259-C-T, CADD 13.10
- R8C (p.Arg8Cys), gnomAD rs2058006754, REVEL 0.22, CADD 16.90
- R8G (p.Arg8Gly), gnomAD rs2058006754
- R8H (p.Arg8His), Ensembl rs2145267929, REVEL 0.22, CADD 22.60
- R8P (p.Arg8Pro), Ensembl rs2145267929
- R8S (p.Arg8Ser), gnomAD rs2058006754, REVEL 0.28, CADD 13.20
- R8W (p.Arg8Trp), rs1193961962, gnomAD 17-39699566-C-T, CADD 4.33
- R8Q (p.Arg8Gln), rs966070730, gnomAD 17-39699567-G-A, CADD 2.95
- R8R (p.Arg8Arg), gnomAD 17-39699568-G-A, CADD 5.07
- R8L (p.Arg8Leu), gnomAD 17-39700261-G-T, REVEL 0.32, CADD 22.50
- W9* (p.Trp9Ter), Ensembl rs2145268149, CADD 38.00
- W9C (p.Trp9Cys), Ensembl rs2145268149, REVEL 0.56, CADD 26.90
- W9S (p.Trp9Ser), Ensembl rs2145268034
- W9R (p.Trp9Arg), rs1211697061, gnomAD 17-39699575-T-A, CADD 3.86
- W9G (p.Trp9Gly), gnomAD 17-39700263-T-G, REVEL 0.44, CADD 25.80
- W9L (p.Trp9Leu), gnomAD 17-39700264-G-T, REVEL 0.39, CADD 23.30
- G10R (p.Gly10Arg), Ensembl rs2145268224, REVEL 0.58, CADD 23.90
- G10V (p.Gly10Val), Ensembl rs2145268260, REVEL 0.46, CADD 23.20
- G10G (p.Gly10Gly), gnomAD 17-39699571-G-C, CADD 7.31
- G10W (p.Gly10Trp), gnomAD 17-39700266-G-T, REVEL 0.55, CADD 24.60
- G10E (p.Gly10Glu), gnomAD 17-39700267-G-A, REVEL 0.55, CADD 23.50
- L11F (p.Leu11Phe), TOPMed rs1456994901, gnomAD rs1456994901, REVEL 0.15, CADD 17.40
- L11H (p.Leu11His), Ensembl rs2145268360
- L11P (p.Leu11Pro), Ensembl rs2145268360, REVEL 0.62, CADD 23.40
- L11R (p.Leu11Arg), Ensembl rs2145268360
- L11V (p.Leu11Val), TOPMed rs1456994901, gnomAD rs1456994901
- L11A (p.Leu11Ala), rs1345424209, gnomAD 17-39700263-T-TG, CADD 32.00
- L11S (p.Leu11Ser), rs1345424209, gnomAD 17-39700263-TG-T, CADD 27.90
- L11I (p.Leu11Ile), gnomAD 17-39700269-C-A, REVEL 0.16, CADD 16.30
- L11L (p.Leu11Leu), gnomAD 17-39700271-C-A, CADD 10.80
- L12F (p.Leu12Phe), gnomAD rs1318994039, REVEL 0.36, CADD 23.00
- L12H (p.Leu12His), Ensembl rs2145268543
- L12I (p.Leu12Ile), gnomAD rs1318994039, REVEL 0.35, CADD 23.60
- L12P (p.Leu12Pro), Ensembl rs2145268543, REVEL 0.64, CADD 28.60
- L12V (p.Leu12Val), gnomAD rs1318994039
- L12L (p.Leu12Leu), rs942061125, gnomAD 17-39700274-C-T, CADD 10.10
- L13F (p.Leu13Phe), Ensembl rs1263781765, REVEL 0.10, CADD 17.40
- L13H (p.Leu13His), Ensembl rs2145268694, REVEL 0.49, CADD 24.10
- L13P (p.Leu13Pro), Ensembl rs2145268694, REVEL 0.65, CADD 23.40
- L13I (p.Leu13Ile), gnomAD 17-39700275-C-A, REVEL 0.10, CADD 16.80
- L13L (p.Leu13Leu), rs921215139, gnomAD 17-39700277-C-T, CADD 12.60
- A14S (p.Ala14Ser), gnomAD rs1442246817, REVEL 0.23, CADD 17.40
- A14T (p.Ala14Thr), gnomAD rs1442246817, REVEL 0.26, CADD 19.90
- A14V (p.Ala14Val), rs1293505485, ClinGen CA399266607, ClinVar RCV003110218, gnomAD rs1293505485, REVEL 0.15, CADD 21.30, Uncertain significance, not provided
- A14P (p.Ala14Pro), gnomAD 17-39700276-TCG-T, CADD 25.70
- A14D (p.Ala14Asp), gnomAD 17-39700279-C-A, REVEL 0.47, CADD 23.50
- A14A (p.Ala14Ala), gnomAD 17-39700280-C-A, CADD 14.30
- L15F (p.Leu15Phe), rs193171026, ClinGen CA158544, cosmic curated COSV54067, ClinVar RCV000120736, REVEL 0.38, CADD 23.60, Likely benign, not provided
- L15H (p.Leu15His), TOPMed rs2058009009, gnomAD rs2058009009, REVEL 0.55, CADD 24.40
- L15I (p.Leu15Ile), 1000Genomes rs193171026, ExAC rs193171026, TOPMed rs193171026, gnomAD rs193171026, REVEL 0.19, CADD 21.70, Likely benign
- L15P (p.Leu15Pro), TOPMed rs2058009009, gnomAD rs2058009009, REVEL 0.63, CADD 24.90
- L15L (p.Leu15Leu), rs2145269055, gnomAD 17-39700283-C-T, CADD 11.60
- L16F (p.Leu16Phe), TOPMed rs1567892325, gnomAD rs1567892325, REVEL 0.42, CADD 23.70, Uncertain significance, not provided
- L16M (p.Leu16Met), gnomAD rs1225599701, REVEL 0.32, CADD 23.60
- L16S (p.Leu16Ser), Ensembl rs2145269169, REVEL 0.46, CADD 24.50
- L16V (p.Leu16Val), gnomAD rs1225599701, REVEL 0.27, CADD 21.30
- L16L (p.Leu16Leu), rs1225599701, gnomAD 17-39700284-T-C, CADD 13.20
- P17A (p.Pro17Ala), TOPMed rs1307888184, gnomAD rs1307888184, REVEL 0.11, CADD 14.30
- P17L (p.Pro17Leu), Ensembl rs2145269330, REVEL 0.15, CADD 20.70
- P17S (p.Pro17Ser), cosmic curated COSV54074, TOPMed rs1307888184, gnomAD rs1307888184, REVEL 0.18, CADD 15.90
- P17T (p.Pro17Thr), TOPMed rs1307888184, gnomAD rs1307888184, REVEL 0.07, CADD 15.50
- P17P (p.Pro17Pro), gnomAD 17-39699565-C-T, CADD 6.67
- P17H (p.Pro17His), gnomAD 17-39699580-GC-G, CADD 3.29
- P17Q (p.Pro17Gln), gnomAD 17-39699582-C-A, CADD 8.58
- P18L (p.Pro18Leu), Ensembl rs2145269487, REVEL 0.27, CADD 20.60
- P18R (p.Pro18Arg), Ensembl rs2145269487, REVEL 0.29, CADD 21.50
- P18S (p.Pro18Ser), TOPMed rs1184958761, REVEL 0.09, CADD 17.80
- P18T (p.Pro18Thr), gnomAD 17-39700290-C-A, REVEL 0.16, CADD 17.40
- P18H (p.Pro18His), gnomAD 17-39700291-C-A, REVEL 0.30, CADD 21.00
- P18P (p.Pro18Pro), rs1227500688, gnomAD 17-39700292-C-G, CADD 13.30
- G19A (p.Gly19Ala), TOPMed rs993479758, REVEL 0.26, CADD 19.60
- G19R (p.Gly19Arg), TOPMed rs1486972911, gnomAD rs1486972911, cosmic curated COSV54073, REVEL 0.33, CADD 22.90
- G19E (p.Gly19Glu), gnomAD 17-39700286-GC-G, CADD 23.80
- G19* (p.Gly19Ter), gnomAD 17-39700293-G-T, CADD 37.00
- G19V (p.Gly19Val), gnomAD 17-39700294-G-T, REVEL 0.32, CADD 22.50
- G19G (p.Gly19Gly), rs2145269715, gnomAD 17-39700295-A-T, CADD 15.70
- A20P (p.Ala20Pro), Ensembl rs2145269807, REVEL 0.35, CADD 22.10
- A20V (p.Ala20Val), rs2145269846, ClinGen CA399266747, ClinVar RCV001881976, Ensembl rs2145269846, REVEL 0.13, CADD 17.00, Uncertain significance, not provided
- A20T (p.Ala20Thr), gnomAD 17-39700296-G-A, REVEL 0.09, CADD 19.90
- A20S (p.Ala20Ser), gnomAD 17-39700296-G-T, REVEL 0.08, CADD 17.30
- A20A (p.Ala20Ala), rs1197332364, gnomAD 17-39700298-C-G, CADD 12.90
- A21G (p.Ala21Gly), rs1004896536, ClinGen CA399266765, ClinVar RCV003846921, TOPMed rs1004896536, AlphaMissense 0.17, MetaLR 0.25, Uncertain significance, not provided
- A21P (p.Ala21Pro), Ensembl rs2145269949
- A21S (p.Ala21Ser), cosmic curated COSV54071, Ensembl rs2145269949, REVEL 0.11, CADD 13.90
- A21T (p.Ala21Thr), Ensembl rs2145269949, REVEL 0.10, CADD 15.90
- A21V (p.Ala21Val), TOPMed rs1004896536, gnomAD rs1004896536, REVEL 0.19, AlphaMissense 0.17, Uncertain significance
- A21E (p.Ala21Glu), gnomAD 17-39700297-CCG-C, CADD 23.80
- A21A (p.Ala21Ala), rs1026011929, gnomAD 17-39700301-G-C, CADD 13.60
- S22C (p.Ser22Cys), Ensembl rs2145270146
- S22G (p.Ser22Gly), Ensembl rs2145270146, REVEL 0.08, CADD 17.90
- S22N (p.Ser22Asn), rs896376245, ClinGen CA290420219, ClinVar RCV001863298, TOPMed rs896376245, REVEL 0.15, CADD 19.70, Uncertain significance, not provided
- S22R (p.Ser22Arg), cosmic curated COSV10879, Ensembl rs2145270146, REVEL 0.14, CADD 16.30
- S22P (p.Ser22Pro), gnomAD 17-39699566-CG-C, CADD 1.34
- S22I (p.Ser22Ile), gnomAD 17-39700303-G-T, REVEL 0.21, CADD 21.60
- S22T (p.Ser22Thr), gnomAD 17-39700303-G-C, REVEL 0.11, CADD 18.50
- S22S (p.Ser22Ser), rs2058011742, gnomAD 17-39700304-C-T, CADD 13.70
- T23I (p.Thr23Ile), TOPMed rs2058012038
- T23S (p.Thr23Ser), TOPMed rs2058012038
- T23A (p.Thr23Ala), gnomAD 17-39700305-A-G, REVEL 0.15, CADD 18.10
- T23N (p.Thr23Asn), gnomAD 17-39700306-C-A, REVEL 0.19, CADD 17.50
- T23T (p.Thr23Thr), rs773744480, gnomAD 17-39700307-C-T, CADD 13.20
- Q24E (p.Gln24Glu), TOPMed rs2058012509, REVEL 0.08, CADD 17.30
- Q24* (p.Gln24Ter), gnomAD 17-39699584-C-T, CADD 6.22
- Q24K (p.Gln24Lys), gnomAD 17-39699584-C-A, CADD 5.57
- Q24R (p.Gln24Arg), gnomAD 17-39699585-A-G, CADD 1.84
- Q24Q (p.Gln24Gln), rs1179865297, gnomAD 17-39699586-A-G, CADD 6.03
- Q24H (p.Gln24His), gnomAD 17-39700310-A-C, REVEL 0.14, CADD 26.10
- V25A (p.Val25Ala), rs755921683, ClinGen CA8533528, ClinVar RCV002019717, ClinVar RCV005017041, REVEL 0.48, CADD 23.60, Uncertain significance, not provided; Gastric cancer; Visceral neuropathy, familial, 2, autosomal recess
- V25E (p.Val25Glu), ExAC rs755921683, TOPMed rs755921683, gnomAD rs755921683, Uncertain significance
- V25G (p.Val25Gly), ExAC rs755921683, TOPMed rs755921683, gnomAD rs755921683, Uncertain significance
- V25L (p.Val25Leu), Ensembl rs2145270441, REVEL 0.51, CADD 33.00
- V25M (p.Val25Met), Ensembl rs2145270441, REVEL 0.56, CADD 34.00
- V25C (p.Val25Cys), gnomAD 17-39700308-CA-C, CADD 27.80
- V25V (p.Val25Val), rs2145403526, gnomAD 17-39706991-G-A, CADD 16.80
- C26G (p.Cys26Gly), Ensembl rs2145403576
- C26S (p.Cys26Ser), Ensembl rs2145403576
- C26W (p.Cys26Trp), TOPMed rs1021403569, gnomAD rs1021403569, Likely benign
- C26Y (p.Cys26Tyr), Ensembl rs2145403619, REVEL 0.93, CADD 27.60
- C26* (p.Cys26Ter), gnomAD 17-39706994-C-A, CADD 35.00
- C26C (p.Cys26Cys), rs1021403569, gnomAD 17-39706994-C-T, CADD 11.50
- T27I (p.Thr27Ile), gnomAD rs1365546088, REVEL 0.23, CADD 20.60
- T27P (p.Thr27Pro), rs779913120, ClinGen CA8533529, ClinVar RCV001893157, ExAC rs779913120, REVEL 0.38, CADD 23.40, Uncertain significance, not provided
- T27S (p.Thr27Ser), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99506, ExAC rs779913120, TOPMed rs779913120, Uncertain significance
- T27T (p.Thr27Thr), rs377542789, gnomAD 17-39706997-C-T, CADD 6.26
- G28A (p.Gly28Ala), gnomAD rs1284110310, REVEL 0.92, CADD 26.50
- G28D (p.Gly28Asp), gnomAD rs1284110310, REVEL 0.93, CADD 27.70
- G28R (p.Gly28Arg), 1000Genomes rs564064363, ExAC rs564064363, TOPMed rs564064363, gnomAD rs564064363, REVEL 0.94, CADD 29.70
- G28S (p.Gly28Ser), 1000Genomes rs564064363, ExAC rs564064363, TOPMed rs564064363, gnomAD rs564064363, REVEL 0.94, CADD 29.00
- G28V (p.Gly28Val), gnomAD rs1284110310
- G28C (p.Gly28Cys), gnomAD 17-39706998-G-T, REVEL 0.93, CADD 31.00
- G28G (p.Gly28Gly), rs528118039, gnomAD 17-39707000-C-T, CADD 11.50
- T29A (p.Thr29Ala), Ensembl rs2145404078
- T29I (p.Thr29Ile), Ensembl rs2145404159
- T29P (p.Thr29Pro), Ensembl rs2145404078
- T29R (p.Thr29Arg), Ensembl rs2145404159
- T29S (p.Thr29Ser), Ensembl rs2145404078
- T29K (p.Thr29Lys), gnomAD 17-39707002-C-A, REVEL 0.81, CADD 25.70
- T29T (p.Thr29Thr), rs2145404221, gnomAD 17-39707003-A-G, CADD 6.49
- D30A (p.Asp30Ala), Ensembl rs2145404332
- D30E (p.Asp30Glu), gnomAD rs2058483158, REVEL 0.35, CADD 18.20, Likely benign
- D30G (p.Asp30Gly), cosmic curated COSV54086, Ensembl rs2145404332
Public ERBB2 analysis runs
- ERBB2 analysis run — ERBB2 (5,694 variants) — completed 2026-07-24
- ERBB2 analysis run — ERBB2 (5,573 variants) — completed 2026-06-18