PLN (Phospholamban) variants and mutations
PLN (also known as Phospholamban) is a human protein-coding gene encoding a phospholamban protein. It tonically restrains SERCA2a-mediated calcium reuptake into the cardiac sarcoplasmic reticulum, with phosphorylation relieving this inhibition during adrenergic stimulation. Pathogenic variants can destabilize calcium cycling and cause dilated or arrhythmogenic cardiomyopathy. This analysis covers 137 PLN variants and mutations. Of these, 91% have computational variant effect predictions. Disease context includes hypertrophic cardiomyopathy, familial isolated dilated cardiomyopathy, and cardiomyopathy. Example PLN variants include M1T, E2D, and E2Q.
Variant analysis overview
- Gene: PLN
- Protein: Phospholamban
- UniProt accession: P26678
- Organism: Homo sapiens
- Variants analyzed: 137
- Variant scope: all variants
- Completed: 2026-08-09
Variant and mutation evidence
- Variant composition: 72 unspecified-consequence records; 33 missense variants; 20 synonymous variants; 8 frameshift variants; 1 in-frame deletions; 2 stop lost; 1 substitution
- Prediction scores: 125 variants have prediction scores (91% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertrophic cardiomyopathy, familial isolated dilated cardiomyopathy, cardiomyopathy, intrinsic cardiomyopathy, Abnormality of the cardiovascular system, dilated cardiomyopathy, Rare familial disorder with hypertrophic cardiomyopathy, atrial fibrillation, Arrhythmogenic right ventricular dysplasia, familial isolated arrhythmogenic ventricular dysplasia, right dominant form, sudden infant death syndrome, cardiac arrest.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 3 post-translational modification sites.
- Structural context: 52 variants have structural context.
- PTM context: 5 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, ClinGen, MaveDB, LitVar.
Notable PLN variants
Examples include M1T, E2D, E2Q, E2K, V4I, V4V, Q5R, Q5P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs727503374, ClinGen CA177643, ClinVar RCV000151663, ClinVar RCV005089739, MetaLR 0.78, MetaSVM 0.72, Conflicting interpretations, Cardiovascular phenotype; not specified; Dilated cardiomyopathy 1P
- E2D (p.Glu2Asp), Ensembl rs1583047436, REVEL 0.18, MetaLR 0.34
- E2Q (p.Glu2Gln), rs758364608, NCI-TCGA Cosmic COSV6264, ExAC rs758364608, REVEL 0.54, MetaLR 0.61, Variant assessed as somatic; moderate impact.
- E2K (p.Glu2Lys), gnomAD 6-118558925-G-A, REVEL 0.58, MetaLR 0.58
- V4I (p.Val4Ile), gnomAD 6-118558931-G-A, REVEL 0.61, MetaLR 0.85
- V4V (p.Val4Val), gnomAD 6-118558933-C-T, CADD 6.58
- Q5R (p.Gln5Arg), rs876657954, ClinGen CA10576677, ClinVar RCV000222681, Ensembl rs876657954, AlphaMissense 0.14, MetaLR 0.76, Uncertain significance, not specified
- Q5P (p.Gln5Pro), gnomAD 6-118558935-A-C, REVEL 0.90, MetaLR 0.78
- Q5H (p.Gln5His), gnomAD 6-118558936-A-C, REVEL 0.77, MetaLR 0.75
- Q5Q (p.Gln5Gln), gnomAD 6-118558936-A-G, CADD 6.98
- Y6D (p.Tyr6Asp), ExAC rs780082801, TOPMed rs780082801, gnomAD rs780082801, REVEL 0.52, MetaLR 0.42, Uncertain significance
- Y6H (p.Tyr6His), rs780082801, ClinGen CA3977968, ClinVar RCV002595829, ExAC rs780082801, REVEL 0.29, MetaLR 0.20, Uncertain significance, Dilated cardiomyopathy 1P
- Y6Y (p.Tyr6Tyr), rs1181173210, gnomAD 6-118558939-C-T, CADD 5.78
- L7L (p.Leu7Leu), rs1583047485, gnomAD 6-118558942-C-T, CADD 9.50
- T8P (p.Thr8Pro), rs1060502977, ClinGen CA16611885, ClinVar RCV000466823, Ensembl rs1060502977, AlphaMissense 0.38, MetaLR 0.82, Uncertain significance, Dilated cardiomyopathy 1P
- T8N (p.Thr8Asn), gnomAD 6-118558944-C-A, REVEL 0.78, MetaLR 0.81
- T8I (p.Thr8Ile), gnomAD 6-118558944-C-T, REVEL 0.80, MetaLR 0.58
- R9C (p.Arg9Cys), rs111033559, ClinGen CA256917, ClinVar RCV000014606, ClinVar RCV000183815, REVEL 0.89, MetaLR 0.84, Pathogenic, not provided; Cardiomyopathy; Dilated cardiomyopathy 1P
- R9H (p.Arg9His), rs754782171, ClinGen CA335497, ClinVar RCV000183816, ClinVar RCV001207506, REVEL 0.91, MetaLR 0.84, Conflicting interpretations, Cardiovascular phenotype; not specified; Dilated cardiomyopathy 1P
- R9L (p.Arg9Leu), UniProt VAR 072926, MetaLR 0.78, MetaSVM 0.70, Likely pathogenic, Dilated cardiomyopathy 1P
- R9G (p.Arg9Gly), gnomAD 6-118558946-C-G, REVEL 0.91, MetaLR 0.78
- R9R (p.Arg9Arg), rs145623013, gnomAD 6-118558948-C-T, CADD 12.60
- S10L (p.Ser10Leu), rs1554219846, ClinGen CA365546051, ClinVar RCV000539278, Ensembl rs1554219846, REVEL 0.68, MetaLR 0.61, Uncertain significance, Dilated cardiomyopathy 1P
- S10A (p.Ser10Ala), gnomAD 6-118558949-T-G, REVEL 0.34, MetaLR 0.48
- S10S (p.Ser10Ser), rs1583047548, gnomAD 6-118558951-A-G, CADD 8.40
- A11G (p.Ala11Gly), NCI-TCGA Cosmic COSV6264, REVEL 0.80, MetaLR 0.85, Variant assessed as somatic; moderate impact.
- A11P (p.Ala11Pro), rs2114969616, ClinGen CA365546054, ClinVar RCV003013219, AlphaMissense 0.36, MetaLR 0.86, Uncertain significance, Dilated cardiomyopathy 1P
- A11T (p.Ala11Thr), rs2114969616, ClinGen CA365546053, ClinVar RCV001888883, Ensembl rs2114969616, AlphaMissense 0.36, MetaLR 0.86, Uncertain significance, Dilated cardiomyopathy 1P
- A11V (p.Ala11Val), NCI-TCGA Cosmic COSV6264, MetaLR 0.85, MetaSVM 0.85, Variant assessed as somatic; moderate impact.
- A11L (p.Ala11Leu), rs1779066083, gnomAD 6-118558943-A-ACT, CADD 28.80
- I12M (p.Ile12Met), rs774556120, ClinGen CA3977971, ClinVar RCV000769215, ClinVar RCV001214646, REVEL 0.37, MetaLR 0.28, Uncertain significance, Dilated cardiomyopathy 1P; Cardiomyopathy
- I12T (p.Ile12Thr), rs771044756, ClinGen CA3977970, ClinVar RCV002455196, ClinVar RCV003234177, REVEL 0.67, MetaLR 0.52, Uncertain significance, Cardiovascular phenotype; not provided; Dilated cardiomyopathy 1P
- I12V (p.Ile12Val), rs749571694, ClinGen CA3977969, ClinVar RCV000214972, ClinVar RCV000229704, REVEL 0.27, MetaLR 0.31, Uncertain significance, Cardiovascular phenotype; Cardiomyopathy; Dilated cardiomyopathy 1P
- R13* (p.Arg13Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R13K (p.Arg13Lys), rs1322414081, ClinGen CA365546093, ClinVar RCV002357459, gnomAD rs1322414081, REVEL 0.88, MetaLR 0.71, Uncertain significance, Cardiovascular phenotype
- R13R (p.Arg13Arg), gnomAD 6-118558958-A-C, CADD 12.80
- R14I (p.Arg14Ile), rs151112761, ClinGen CA3977972, ClinVar RCV000551751, ClinVar RCV002330878, REVEL 0.92, MetaLR 0.86, Uncertain significance, not provided; Dilated cardiomyopathy 1P; Cardiovascular phenotype
- R14del (p.Arg14del), rs397516784, gnomAD 6-118558956-TAAG-, CADD 20.70
- R14R (p.Arg14Arg), gnomAD 6-118558961-A-C, CADD 13.70
- A15T (p.Ala15Thr), rs397516785, ClinGen CA134581, ClinVar RCV000037583, ClinVar RCV001852781, AlphaMissense 0.30, MetaLR 0.84, Conflicting interpretations, not specified; Dilated cardiomyopathy 1P
- A15V (p.Ala15Val), TOPMed rs1779068742, MetaLR 0.83, MetaSVM 0.81
- S16S (p.Ser16Ser), gnomAD 6-118558969-A-C, CADD 7.50
- T17A (p.Thr17Ala), gnomAD 6-118558970-A-G, REVEL 0.36, MetaLR 0.51
- T17I (p.Thr17Ile), gnomAD 6-118558971-C-T, REVEL 0.39, MetaLR 0.42
- T17T (p.Thr17Thr), rs996756205, gnomAD 6-118558972-C-A, CADD 8.57
- I18T (p.Ile18Thr), rs1029766634, ClinGen CA146529607, ClinVar RCV000695526, ClinVar RCV001798961, REVEL 0.75, MetaLR 0.53, Uncertain significance, Dilated cardiomyopathy 1P; Hypertrophic cardiomyopathy 18; Cardiovascular phenot
- I18M (p.Ile18Met), gnomAD 6-118558975-T-G, REVEL 0.31, MetaLR 0.35
- E19D (p.Glu19Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E19G (p.Glu19Gly), rs2114969791, ClinGen CA365546191, ClinVar RCV001921033, ClinVar RCV002344034, AlphaMissense 0.25, MetaLR 0.58, Uncertain significance, Dilated cardiomyopathy 1P; Cardiovascular phenotype
- E19E (p.Glu19Glu), gnomAD 6-118558978-A-G, CADD 10.60
- M20T (p.Met20Thr), gnomAD 6-118558980-T-C, REVEL 0.42, MetaLR 0.43
- M20I (p.Met20Ile), gnomAD 6-118558981-G-T, REVEL 0.30, MetaLR 0.32
- P21S (p.Pro21Ser), rs397516786, ClinGen CA365546219, ClinVar RCV001330958, ClinVar RCV006557374, REVEL 0.42, MetaLR 0.46, Uncertain significance, Dilated cardiomyopathy 1P; Hypertrophic cardiomyopathy 18
- P21T (p.Pro21Thr), rs397516786, ClinGen CA134584, ClinVar RCV000037584, ClinVar RCV001237789, REVEL 0.45, MetaLR 0.45, Uncertain significance, Cardiovascular phenotype; Dilated cardiomyopathy 1P; Hypertrophic cardiomyopathy
- Q22L (p.Gln22Leu), rs794729138, gnomAD 6-118558982-C-CCT, CADD 28.80
- Q22H (p.Gln22His), gnomAD 6-118558987-A-T, REVEL 0.45, MetaLR 0.32
- Q23E (p.Gln23Glu), rs876657955, ClinGen CA10576678, ClinVar RCV000216465, Ensembl rs876657955, AlphaMissense 0.06, MetaLR 0.58, Uncertain significance, not specified
- Q23R (p.Gln23Arg), TOPMed rs1779070557, MetaLR 0.53, MetaSVM -0.03
- Q23H (p.Gln23His), gnomAD 6-118558987-ACAAG, CADD 32.00
- Q23P (p.Gln23Pro), gnomAD 6-118558989-A-C, REVEL 0.86, MetaLR 0.54
- Q23Q (p.Gln23Gln), rs775923421, gnomAD 6-118558990-A-G, CADD 8.34
- R25C (p.Arg25Cys), rs761056344, ClinGen CA335503, NCI-TCGA Cosmic COSV1006, NCI-TCGA Cosmic COSV6264, REVEL 0.64, MetaLR 0.68, Conflicting interpretations, Cardiovascular phenotype; not provided; Dilated cardiomyopathy 1P
- R25G (p.Arg25Gly), rs761056344, ClinGen CA335499, ClinVar RCV000183817, ClinVar RCV001852372, REVEL 0.71, MetaLR 0.54, Uncertain significance, not provided; Dilated cardiomyopathy 1P
- R25H (p.Arg25His), rs1004405095, ClinGen CA16611886, ClinVar RCV000460010, ClinVar RCV000786193, REVEL 0.66, MetaLR 0.68, Uncertain significance, Cardiovascular phenotype; not provided; Dilated cardiomyopathy 1P
- R25S (p.Arg25Ser), NCI-TCGA Cosmic COSV1006, NCI-TCGA Cosmic COSV6264, REVEL 0.68, MetaLR 0.51, Variant assessed as somatic; moderate impact.
- Q26K (p.Gln26Lys), gnomAD 6-118558997-C-A, REVEL 0.54, MetaLR 0.73
- K27E (p.Lys27Glu), rs2114969956, ClinGen CA365546331, ClinVar RCV002050246, Ensembl rs2114969956, AlphaMissense 0.13, MetaLR 0.29, Uncertain significance, Dilated cardiomyopathy 1P
- K27N (p.Lys27Asn), Ensembl rs1583047807, MetaLR 0.09, MetaSVM -0.87
- K27S (p.Lys27Ser), gnomAD 6-118558997-CA-C, CADD 27.40
- L28I (p.Leu28Ile), gnomAD 6-118559003-C-A, REVEL 0.29, MetaLR 0.48
- L28Q (p.Leu28Gln), gnomAD 6-118559004-T-A, REVEL 0.71, MetaLR 0.58
- Q29* (p.Gln29Ter), rs1779072006, ClinGen CA365546360, ClinVar RCV001221395, ClinVar RCV004032418, Pathogenic
- Q29H (p.Gln29His), rs1779072179, ClinGen CA365546367, ClinVar RCV003368294, TOPMed rs1779072179, REVEL 0.71, MetaLR 0.81, Uncertain significance, Cardiovascular phenotype
- Q29K (p.Gln29Lys), gnomAD 6-118559006-C-A, REVEL 0.68, MetaLR 0.76
- Q29P (p.Gln29Pro), gnomAD 6-118559007-A-C, REVEL 0.84, MetaLR 0.78
- Q29Q (p.Gln29Gln), gnomAD 6-118559008-G-A, CADD 5.04
- N30* (p.Asn30Ter), gnomAD 6-118559008-G-GT, CADD 26.70
- N30Y (p.Asn30Tyr), gnomAD 6-118559009-A-T, REVEL 0.49, MetaLR 0.27
- N30N (p.Asn30Asn), rs868301643, gnomAD 6-118559011-T-C, CADD 3.90
- L31I (p.Leu31Ile), NCI-TCGA TCGA novel, REVEL 0.72, MetaLR 0.79, Variant assessed as somatic; moderate impact.
- L31V (p.Leu31Val), gnomAD 6-118559012-C-G, REVEL 0.81, MetaLR 0.79
- F32L (p.Phe32Leu), rs1489656774, ClinGen CA365546403, ClinVar RCV003628192, gnomAD rs1489656774, REVEL 0.82, MetaLR 0.77, Uncertain significance, Dilated cardiomyopathy 1P
- I33F (p.Ile33Phe), TOPMed rs1779072875
- I33M (p.Ile33Met), NCI-TCGA Cosmic COSV6264, MetaLR 0.41, MetaSVM -0.22, Variant assessed as somatic; moderate impact.
- N34H (p.Asn34His), Ensembl rs745592199, MetaLR 0.82, MetaSVM 0.84
- N34N (p.Asn34Asn), gnomAD 6-118559023-T-C, CADD 2.73
- F35L (p.Phe35Leu), NCI-TCGA TCGA novel, TOPMed rs1779073411, Variant assessed as somatic; moderate impact.
- F35V (p.Phe35Val), NCI-TCGA Cosmic COSV1006, MetaLR 0.79, MetaSVM 0.75, Variant assessed as somatic; moderate impact.
- F35I (p.Phe35Ile), gnomAD 6-118559024-T-A, REVEL 0.87, MetaLR 0.79
- C36R (p.Cys36Arg), gnomAD 6-118559027-T-C, REVEL 0.80, MetaLR 0.55
- C36Y (p.Cys36Tyr), gnomAD 6-118559028-G-A, REVEL 0.78, MetaLR 0.60
- L37F (p.Leu37Phe), TOPMed rs1266890278, gnomAD rs1266890278, MetaLR 0.87, MetaSVM 0.89
- L37V (p.Leu37Val), TOPMed rs1266890278, gnomAD rs1266890278, REVEL 0.81, MetaLR 0.85
- I38M (p.Ile38Met), rs2534333802, ClinGen CA365546560, ClinVar RCV002346612, Uncertain significance, Cardiovascular phenotype
- I38T (p.Ile38Thr), rs1554219862, ClinGen CA365546538, ClinVar RCV000639860, Ensembl rs1554219862, REVEL 0.84, MetaLR 0.78, Uncertain significance, Dilated cardiomyopathy 1P
- I38L (p.Ile38Leu), gnomAD 6-118559033-A-C, REVEL 0.69, MetaLR 0.62
- L39* (p.Leu39Ter), rs111033560, ClinGen CA249977, ClinVar RCV000014607, ClinVar RCV000022712, CADD 37.00, Pathogenic
- L39L (p.Leu39Leu), gnomAD 6-118559036-T-C, CADD 6.99
- I40L (p.Ile40Leu), Ensembl rs1779074440, MetaLR 0.61, MetaSVM 0.35
- I40V (p.Ile40Val), gnomAD 6-118559039-A-G, REVEL 0.63, MetaLR 0.61
- I40T (p.Ile40Thr), gnomAD 6-118559040-T-C, REVEL 0.86, MetaLR 0.78
- I40M (p.Ile40Met), gnomAD 6-118559041-A-G, REVEL 0.71, MetaLR 0.71
- C41S (p.Cys41Ser), rs2534333917, ClinGen CA365546591, ClinVar RCV003037184, REVEL 0.90, MetaLR 0.82, Uncertain significance, Dilated cardiomyopathy 1P
- L42F (p.Leu42Phe), NCI-TCGA Cosmic COSV6264, Variant assessed as somatic; moderate impact.
- L42I (p.Leu42Ile), rs2114970183, ClinGen CA365546645, NCI-TCGA Cosmic COSV6264, ClinVar RCV001883333, AlphaMissense 0.24, MetaLR 0.84, Uncertain significance, Dilated cardiomyopathy 1P
- L42L (p.Leu42Leu), gnomAD 6-118559047-C-T, CADD 5.61
- L43A (p.Leu43Ala), rs1779074612, ClinGen CA1093656688, ClinVar RCV002430343, ClinVar RCV003099900, Uncertain significance
- L43F (p.Leu43Phe), rs2534334022, ClinGen CA365546675, ClinVar RCV003628221, Uncertain significance, Dilated cardiomyopathy 1P
- L43W (p.Leu43Trp), gnomAD 6-118559049-T-G, REVEL 0.87, MetaLR 0.85
- L43L (p.Leu43Leu), gnomAD 6-118559050-G-A, CADD 7.75
- L44M (p.Leu44Met), NCI-TCGA TCGA novel, REVEL 0.69, MetaLR 0.81, Variant assessed as somatic; moderate impact.
- L44P (p.Leu44Pro), rs794729210, ClinGen CA275472, ClinVar RCV000184030, ClinVar RCV001852380, REVEL 0.94, MetaLR 0.85, Uncertain significance, Cardiovascular phenotype; Dilated cardiomyopathy 1P
- I45L (p.Ile45Leu), gnomAD 6-118559054-A-C, REVEL 0.69, MetaLR 0.61
- C46F (p.Cys46Phe), Ensembl rs2114970255, REVEL 0.72, MetaLR 0.60
- C46R (p.Cys46Arg), rs2534334077, ClinGen CA365546704, ClinVar RCV003627284, REVEL 0.86, MetaLR 0.55, Uncertain significance, Dilated cardiomyopathy 1P
- I47M (p.Ile47Met), rs552078051, ClinGen CA3977976, ClinVar RCV001917766, 1000Genomes rs552078051, REVEL 0.80, MetaLR 0.73, Uncertain significance, Dilated cardiomyopathy 1P
- I47V (p.Ile47Val), NCI-TCGA Cosmic COSV1006, MetaLR 0.61, MetaSVM 0.35, Variant assessed as somatic; moderate impact.
- I47Y (p.Ile47Tyr), gnomAD 6-118559058-G-GT, CADD 33.00
- I47T (p.Ile47Thr), gnomAD 6-118559061-T-C, REVEL 0.90, MetaLR 0.78
- I48S (p.Ile48Ser), rs1064796276, ClinGen CA16618234, ClinVar RCV000481635, ClinVar RCV005628255, Uncertain significance, Dilated cardiomyopathy 1P
- I48T (p.Ile48Thr), gnomAD 6-118559064-T-C, REVEL 0.89, MetaLR 0.78
- I48I (p.Ile48Ile), rs141114252, gnomAD 6-118559065-C-T, CADD 2.73
- V49M (p.Val49Met), rs749962743, ClinGen CA335494, ClinVar RCV001309721, ClinVar RCV001704888, REVEL 0.88, MetaLR 0.84, Uncertain significance, Cardiovascular phenotype; Dilated cardiomyopathy 1P; Hypertrophic cardiomyopathy
- V49V (p.Val49Val), gnomAD 6-118559068-G-T, CADD 7.71
- M50I (p.Met50Ile), rs2534334328, ClinGen CA365546778, ClinVar RCV003306374, REVEL 0.62, MetaLR 0.51, Uncertain significance, Cardiovascular phenotype
- M50L (p.Met50Leu), rs757797900, ClinGen CA3977978, ClinVar RCV000770227, ExAC rs757797900, REVEL 0.40, MetaLR 0.47, Uncertain significance, Cardiomyopathy
- M50T (p.Met50Thr), rs1779076744, ClinGen CA365546776, ClinVar RCV001316405, ClinVar RCV001799063, REVEL 0.79, MetaLR 0.46, Uncertain significance, Cardiomyopathy; Dilated cardiomyopathy 1P
- L51F (p.Leu51Phe), rs766452369, ClinGen CA3977979, ClinVar RCV001773301, ClinVar RCV005095045, REVEL 0.74, AlphaMissense 0.12, Uncertain significance, not provided; Dilated cardiomyopathy 1P
- L51I (p.Leu51Ile), rs766452369, ClinGen CA365546789, ClinVar RCV001041423, ExAC rs766452369, AlphaMissense 0.12, MetaLR 0.86, Uncertain significance, Dilated cardiomyopathy 1P
- L51P (p.Leu51Pro), rs397516783, ClinGen CA134573, ClinVar RCV000037579, ClinVar RCV002513479, REVEL 0.94, MetaLR 0.85, Uncertain significance, not specified; Dilated cardiomyopathy 1P
- L51Q (p.Leu51Gln), gnomAD 6-118559072-CTTCT, CADD 32.00
- L52I (p.Leu52Ile), rs2114970391, ClinGen CA365546796, ClinVar RCV001368208, ClinVar RCV002404877, REVEL 0.48, MetaLR 0.61, Uncertain significance, Cardiovascular phenotype; Dilated cardiomyopathy 1P
- L52S (p.Leu52Ser), gnomAD 6-118559072-C-CT, CADD 32.00
Public PLN analysis runs
- PLN analysis run — PLN (137 variants) — completed 2026-08-09