PRKAR1A (P10644) variants and mutations
PRKAR1A (also known as P10644) is a human protein-coding gene encoding a cAMP-dependent protein kinase type I-alpha regulatory subunit protein. It restrains protein kinase A activity in the absence of cyclic AMP and thereby controls a wide range of endocrine and growth signals. Germline loss-of-function variants cause Carney complex, with endocrine overactivity, spotty pigmentation, myxomas, and multiple tumor predispositions. This analysis covers 875 PRKAR1A variants and mutations. Of these, 56% have computational variant effect predictions. Disease context includes Carney complex, type 1, Acrodysostosis 1 with or without hormone resistance, and Carney complex. Example PRKAR1A variants include M1I, M1V, and E2D.
Variant analysis overview
- Gene: PRKAR1A
- Protein: P10644
- UniProt accession: P10644
- Organism: Homo sapiens
- Variants analyzed: 875
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 733 unspecified-consequence records; 95 synonymous variants; 36 missense variants; 5 in-frame deletions; 3 frameshift variants; 1 splice-region variants; 2 substitution
- Prediction scores: 494 variants have prediction scores (56% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Carney complex, type 1, Acrodysostosis 1 with or without hormone resistance, Carney complex, acrodysostosis, pigmented nodular adrenocortical disease, primary, 1, familial atrial myxoma, amelogenesis imperfecta type 1G, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, cancer, malignant endocrine neoplasm, adrenal cortex carcinoma.
Protein structure and variant hotspots
- Protein features: 16 binding sites; 7 post-translational modification sites.
- PTM context: 21 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 PRKAR1A variants
Examples include M1I, M1V, E2D, E2Q, E2V, S3C, S3F, S3P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2509357138, ClinGen CA400751757, ClinVar RCV004516153, Likely pathogenic, Hereditary cancer-predisposing syndrome
- M1V (p.Met1Val), rs281864779, ClinGen CA341227, ClinVar RCV000013505, ClinVar RCV000523178, MetaLR 0.51, MetaSVM 0.12, Pathogenic, Hereditary cancer-predisposing syndrome; not provided; Carney complex, type 1
- E2D (p.Glu2Asp), Ensembl rs2143148382
- E2Q (p.Glu2Gln), rs1600461762, ClinGen CA400751761, ClinVar RCV000804490, ClinVar RCV004944176, CADD 23.90, PolyPhen-2 0.06, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- E2V (p.Glu2Val), cosmic curated COSV62236
- S3C (p.Ser3Cys), ExAC rs752643409, TOPMed rs752643409, gnomAD rs752643409, AlphaMissense 0.09, MetaLR 0.67
- S3F (p.Ser3Phe), rs752643409, ClinGen CA400751772, ClinVar RCV004516163, AlphaMissense 0.09, MetaLR 0.67, Uncertain significance, Hereditary cancer-predisposing syndrome
- S3P (p.Ser3Pro), rs1488444958, ClinGen CA400751769, ClinVar RCV004516159, TOPMed rs1488444958, CADD 23.10, PolyPhen-2 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome
- S3T (p.Ser3Thr), cosmic curated COSV62235
- G4C (p.Gly4Cys), rs2143148487, ClinGen CA400751775, ClinVar RCV003034997, Ensembl rs2143148487, AlphaMissense 0.11, MetaLR 0.47, Uncertain significance, Carney complex, type 1
- G4D (p.Gly4Asp), cosmic curated COSV62236, CADD 22.50, PolyPhen-2 0.01, Uncertain significance, Carney complex, type 1
- G4F (p.Gly4Phe), rs2143148523, ClinGen CA2573154854, ClinVar RCV002038024, Ensembl rs2143148523, Uncertain significance, Carney complex, type 1
- G4G (p.Gly4Gly), rs2143148544, gnomAD 17-68515411-C-T, CADD 14.00
- S5G (p.Ser5Gly), rs1600461789, ClinGen CA400751780, ClinVar RCV001011392, ClinVar RCV003514453, CADD 21.90, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1; not specified
- S5N (p.Ser5Asn), Ensembl rs2085399576
- S5R (p.Ser5Arg), rs1600461789, ClinGen CA400751779, ClinVar RCV000797705, ClinVar RCV004569551, CADD 22.50, PolyPhen-2 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1; Acrodysostosis
- T6I (p.Thr6Ile), Ensembl rs2143148718
- T6P (p.Thr6Pro), Ensembl rs1600461810
- T6T (p.Thr6Thr), rs755978926, gnomAD 17-68515417-C-T, CADD 1.35
- A7P (p.Ala7Pro), ESP rs369210646, ExAC rs369210646, TOPMed rs369210646, gnomAD rs369210646, Benign
- A7S (p.Ala7Ser), cosmic curated COSV62235, ESP rs369210646, ExAC rs369210646, TOPMed rs369210646, Benign
- A7T (p.Ala7Thr), rs369210646, ClinGen CA8729138, cosmic curated COSV10442, ClinVar RCV000562330, CADD 6.61, PolyPhen-2 0.00, Conflicting interpretations, not specified; Carney complex, type 1; Hereditary cancer-predisposing syndrome
- A7V (p.Ala7Val), cosmic curated COSV10943, NCI-TCGA TCGA novel, Uncertain significance, Hereditary cancer-predisposing syndrome
- A7D (p.Ala7Asp), gnomAD 17-68515419-C-A, CADD 16.00, PolyPhen-2 0.00
- A7A (p.Ala7Ala), rs753565093, gnomAD 17-68515420-C-T, CADD 5.42
- A8D (p.Ala8Asp), rs2085400226, ClinGen CA400751801, ClinVar RCV001210388, Ensembl rs2085400226, AlphaMissense 0.09, MetaLR 0.45, Uncertain significance, Carney complex, type 1
- A8T (p.Ala8Thr), rs1224297486, ClinGen CA400751798, ClinVar RCV001221178, ClinVar RCV002447114, CADD 8.83, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- A8V (p.Ala8Val), rs2085400226, ClinGen CA400751803, ClinVar RCV001371600, Ensembl rs2085400226, AlphaMissense 0.09, MetaLR 0.45, Uncertain significance, Carney complex, type 1
- A8S (p.Ala8Ser), gnomAD 17-68515421-G-T, CADD 7.05, PolyPhen-2 0.00
- A8A (p.Ala8Ala), rs561158629, gnomAD 17-68515423-C-T, CADD 13.50
- S9G (p.Ser9Gly), rs778468626, ClinGen CA400751805, ClinVar RCV000791638, ClinVar RCV002249500, CADD 14.40, PolyPhen-2 0.00, Uncertain significance, Familial atrial myxoma; Pigmented nodular adrenocortical disease, primary, 1; Ca
- S9N (p.Ser9Asn), UniProt VAR 046894, CADD 16.40, PolyPhen-2 0.00, Pathogenic, in CNC1
- S9R (p.Ser9Arg), rs745391692, ClinGen CA8729142, ClinVar RCV000781768, ClinVar RCV001016643, CADD 15.40, PolyPhen-2 0.04, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Carney complex, type 1
- E10D (p.Glu10Asp), cosmic curated COSV10067, Uncertain significance, Hereditary cancer-predisposing syndrome
- E10K (p.Glu10Lys), rs1467886544, ClinGen CA400751810, ClinVar RCV001128516, ClinVar RCV001128517, CADD 23.70, PolyPhen-2 0.20, Uncertain significance, Acrodysostosis 1 with or without hormone resistance; Hereditary cancer-predispos
- E11D (p.Glu11Asp), rs2085400700, ClinGen CA400751824, ClinVar RCV001297977, ClinVar RCV003294212, CADD 17.00, PolyPhen-2 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- A12G (p.Ala12Gly), rs1292133703, ClinGen CA400751830, ClinVar RCV000818013, ClinVar RCV002285417, CADD 22.00, PolyPhen-2 0.04, Uncertain significance, not provided; Carney complex, type 1; Hereditary cancer-predisposing syndrome
- A12T (p.Ala12Thr), Ensembl rs2143149344
- A12V (p.Ala12Val), TOPMed rs1292133703, CADD 22.50, PolyPhen-2 0.11, Uncertain significance
- R13C (p.Arg13Cys), rs1177674637, ClinGen CA400751832, ClinVar RCV001225158, ClinVar RCV002356956, CADD 24.80, PolyPhen-2 0.46, Uncertain significance, Acrodysostosis 1 with or without hormone resistance; Hereditary cancer-predispos
- R13G (p.Arg13Gly), TOPMed rs1177674637, gnomAD rs1177674637, CADD 21.00, PolyPhen-2 0.03, Uncertain significance, Hereditary cancer-predisposing syndrome
- R13H (p.Arg13His), rs2143149544, ClinGen CA400751835, NCI-TCGA Cosmic COSV6223, cosmic curated COSV62235, CADD 24.30, PolyPhen-2 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Carney complex, type 1
- S14G (p.Ser14Gly), rs2509357630, ClinGen CA400751839, ClinVar RCV003515782, CADD 22.30, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- S14I (p.Ser14Ile), cosmic curated COSV10067
- S14N (p.Ser14Asn), cosmic curated COSV10969, gnomAD rs757185291
- S14T (p.Ser14Thr), gnomAD rs757185291, CADD 22.50, PolyPhen-2 0.04, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- S14S (p.Ser14Ser), rs2143149658, gnomAD 17-68515441-C-T, CADD 15.20
- L15F (p.Leu15Phe), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62235, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- L15I (p.Leu15Ile), rs2143149707, ClinGen CA400751845, ClinVar RCV001367352, ClinVar RCV003298596, AlphaMissense 0.17, MetaLR 0.44, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- L15P (p.Leu15Pro), rs2509357685, ClinGen CA400751848, ClinVar RCV002328694, Uncertain significance, Hereditary cancer-predisposing syndrome
- R16* (p.Arg16Ter), rs886041228, ClinGen CA10603402, ClinVar RCV000265264, ClinVar RCV000558438, AlphaMissense 0.26, MetaLR 0.46, Pathogenic
- R16G (p.Arg16Gly), rs886041228, ClinGen CA400751851, ClinVar RCV003091914, ClinVar RCV003294497, AlphaMissense 0.26, MetaLR 0.46, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Carney complex, type 1
- R16Q (p.Arg16Gln), rs2085401218, ClinGen CA400751852, cosmic curated COSV62235, ClinVar RCV001341395, AlphaMissense 0.10, MetaLR 0.40, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; Carney complex, type 1
- R16R (p.Arg16Arg), rs886041228, gnomAD 17-68515445-C-A, AlphaMissense 0.26, MetaLR 0.46
- E17D (p.Glu17Asp), rs771518581, ClinGen CA8729143, cosmic curated COSV10969, ClinVar RCV001023706, CADD 18.80, PolyPhen-2 0.69, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Carney complex, type 1
- E17Q (p.Glu17Gln), TOPMed rs2085401294
- E17V (p.Glu17Val), Ensembl rs2143149969
- E17E (p.Glu17Glu), gnomAD 17-68515450-A-G, CADD 13.60
- C18Y (p.Cys18Tyr), Ensembl rs1172984891
- E19A (p.Glu19Ala), ExAC rs780569077, gnomAD rs780569077, CADD 27.60, PolyPhen-2 0.55
- E19E (p.Glu19Glu), rs1418080546, gnomAD 17-68515456-G-A, CADD 15.20
- L20F (p.Leu20Phe), cosmic curated COSV10606, CADD 22.50, PolyPhen-2 0.04, Uncertain significance, Carney complex, type 1
- L20I (p.Leu20Ile), rs2509357857, ClinGen CA400751879, ClinVar RCV003515565, ClinVar RCV004368994, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- L20P (p.Leu20Pro), rs1600461989, ClinGen CA400751881, ClinVar RCV003880103, Ensembl rs1600461989, AlphaMissense 0.10, MetaLR 0.23, Uncertain significance, Carney complex, type 1
- L20R (p.Leu20Arg), rs1600461989, ClinGen CA400751882, ClinVar RCV001024779, ClinVar RCV005253682, AlphaMissense 0.10, MetaLR 0.23, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- L20L (p.Leu20Leu), rs372451862, gnomAD 17-68515459-C-T, CADD 16.70
- Y21* (p.Tyr21Ter), cosmic curated COSV10591
- Y21C (p.Tyr21Cys), rs2143150295, ClinGen CA400751886, ClinVar RCV001763846, ClinVar RCV003626685, CADD 31.00, PolyPhen-2 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Carney complex, type 1
- Y21H (p.Tyr21His), ExAC rs769019433, gnomAD rs769019433, CADD 29.30, PolyPhen-2 0.98
- Y21Y (p.Tyr21Tyr), rs777110464, gnomAD 17-68515462-C-T, CADD 2.68
- V22A (p.Val22Ala), TOPMed rs2085402151, Uncertain significance
- V22F (p.Val22Phe), rs878854561, ClinGen CA10583669, ClinVar RCV000232417, ClinVar RCV004658996, AlphaMissense 0.17, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- V22G (p.Val22Gly), rs2085402151, ClinGen CA400751893, ClinVar RCV001304701, TOPMed rs2085402151, AlphaMissense 0.94, MetaLR 0.63, Uncertain significance, Carney complex, type 1
- V22I (p.Val22Ile), rs878854561, ClinGen CA400751890, ClinVar RCV001231257, ClinVar RCV003373063, AlphaMissense 0.17, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- V22L (p.Val22Leu), gnomAD 17-68515463-G-C, CADD 22.50, PolyPhen-2 0.01
- V22V (p.Val22Val), rs748395923, gnomAD 17-68515465-C-G, CADD 15.60
- Q23R (p.Gln23Arg), ExAC rs770156593, CADD 23.10, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q23Q (p.Gln23Gln), rs773518851, gnomAD 17-68515468-G-A, CADD 21.30
- K24Q (p.Lys24Gln), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62235, Variant assessed as somatic; moderate impact.
- K24R (p.Lys24Arg), rs763158372, ClinGen CA8729151, ClinVar RCV000466415, ClinVar RCV001026146, CADD 22.80, PolyPhen-2 0.00, Uncertain significance, Acrodysostosis 1 with or without hormone resistance; Hereditary cancer-predispos
- K24K (p.Lys24Lys), rs1389740572, gnomAD 17-68515471-G-A, CADD 19.70
- H25N (p.His25Asn), ESP rs140795787, ExAC rs140795787, TOPMed rs140795787, gnomAD rs140795787, Uncertain significance
- H25Q (p.His25Gln), rs2143150732, ClinGen CA400751915, ClinVar RCV004516157, ClinVar RCV006488686, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- H25Y (p.His25Tyr), rs140795787, ClinGen CA8729152, ClinVar RCV000818450, ClinVar RCV001026388, CADD 23.50, PolyPhen-2 0.11, Uncertain significance, Acrodysostosis 1 with or without hormone resistance; Carney complex, type 1; Her
- H25R (p.His25Arg), gnomAD 17-68515473-A-G, CADD 22.70, PolyPhen-2 0.07
- H25H (p.His25His), rs2143150732, gnomAD 17-68515474-T-C, CADD 18.90
- N26D (p.Asn26Asp), rs774277428, ClinGen CA8729153, ClinVar RCV001933690, ClinVar RCV002397929, CADD 22.90, PolyPhen-2 0.36, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- N26K (p.Asn26Lys), Ensembl rs2143150814, Uncertain significance, Pigmented nodular adrenocortical disease, primary, 1; Acrodysostosis 1 with or w
- N26S (p.Asn26Ser), cosmic curated COSV10067, Uncertain significance, Hereditary cancer-predisposing syndrome
- N26T (p.Asn26Thr), rs2143150787, ClinGen CA400751918, cosmic curated COSV10067, ClinVar RCV001370397, AlphaMissense 0.35, MetaLR 0.55, Uncertain significance, Carney complex, type 1
- I27M (p.Ile27Met), rs1235317386, ClinGen CA400751929, ClinVar RCV000575969, ClinVar RCV001853793, AlphaMissense 0.63, MetaLR 0.68, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- I27V (p.Ile27Val), rs2509358164, ClinGen CA400751924, ClinVar RCV002419132, ClinVar RCV003099809, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- I27I (p.Ile27Ile), rs1235317386, gnomAD 17-68515480-T-C, AlphaMissense 0.63, MetaLR 0.68
- Q28* (p.Gln28Ter), rs281864780, ClinGen CA344454, cosmic curated COSV10067, ClinVar RCV000034296, AlphaMissense 0.36, MetaLR 0.50, Likely pathogenic
- Q28E (p.Gln28Glu), rs281864780, ClinGen CA400751930, ClinVar RCV001226660, ClinVar RCV002429962, AlphaMissense 0.36, MetaLR 0.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- Q28P (p.Gln28Pro), rs1600462191, ClinGen CA400751932, ClinVar RCV001017705, ClinVar RCV002304225, AlphaMissense 0.61, MetaLR 0.66, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- A29P (p.Ala29Pro), rs760726941, ClinGen CA400751938, ClinVar RCV002447988, AlphaMissense 0.08, MetaLR 0.23, Uncertain significance, Hereditary cancer-predisposing syndrome
- A29S (p.Ala29Ser), rs760726941, ClinGen CA8729154, ClinVar RCV000553000, ExAC rs760726941, AlphaMissense 0.08, MetaLR 0.23, Uncertain significance, Carney complex, type 1
- A29T (p.Ala29Thr), ExAC rs760726941, gnomAD rs760726941, Uncertain significance
- A29V (p.Ala29Val), rs763929951, ClinGen CA8729155, ClinVar RCV000812651, ClinVar RCV002372282, CADD 22.10, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- A29A (p.Ala29Ala), rs3730349, gnomAD 17-68515486-G-A, CADD 2.66
- L30V (p.Leu30Val), gnomAD rs1202375076, CADD 19.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- L30P (p.Leu30Pro), gnomAD 17-68515488-T-C, CADD 27.50, PolyPhen-2 0.96
- L31F (p.Leu31Phe), rs2143151261, ClinGen CA400751948, ClinVar RCV001938562, Ensembl rs2143151261, CADD 23.90, PolyPhen-2 0.65, Uncertain significance, Carney complex, type 1
- L31H (p.Leu31His), Ensembl rs2143151315
- L31L (p.Leu31Leu), rs891869550, gnomAD 17-68515492-C-T, CADD 14.50
- K32E (p.Lys32Glu), rs756985434, ClinGen CA8729157, ClinVar RCV000556130, ClinVar RCV002377115, CADD 29.00, PolyPhen-2 0.98, Uncertain significance, Acrodysostosis 1 with or without hormone resistance; Carney complex, type 1; Her
- K32R (p.Lys32Arg), rs1176097601, ClinGen CA400751955, ClinVar RCV002385278, ClinVar RCV003094837, CADD 25.30, PolyPhen-2 0.98, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- K32T (p.Lys32Thr), cosmic curated COSV10591
- K32K (p.Lys32Lys), gnomAD 17-68515495-A-G, CADD 18.40
- D33G (p.Asp33Gly), rs2085404026, ClinGen CA400751963, ClinVar RCV001977235, ClinVar RCV005465658, CADD 31.00, PolyPhen-2 0.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- D33N (p.Asp33Asn), rs2085403956, ClinGen CA400751959, ClinVar RCV002024253, ClinVar RCV003303659, CADD 23.90, PolyPhen-2 0.36, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- D33D (p.Asp33Asp), rs184088832, gnomAD 17-68515498-T-C, CADD 6.50
- S34A (p.Ser34Ala), gnomAD rs1257543736, CADD 22.70, PolyPhen-2 0.00
- S34C (p.Ser34Cys), rs944887425, ClinGen CA293327597, ClinVar RCV000704942, ClinVar RCV001009718, CADD 19.80, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Acrodysostosis 1 with or without hormon
- S34F (p.Ser34Phe), gnomAD 17-68515500-C-T, CADD 24.20, PolyPhen-2 0.06
- I35V (p.Ile35Val), rs377513504, ClinGen CA8729158, cosmic curated COSV62236, ClinVar RCV000323950, CADD 22.20, PolyPhen-2 0.05, Conflicting interpretations, not specified; not provided; Carney complex, type 1
- V36G (p.Val36Gly), rs1600462346, ClinGen CA400751983, ClinVar RCV001009840, Ensembl rs1600462346, CADD 23.90, PolyPhen-2 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome
- V36L (p.Val36Leu), TOPMed rs1215353269
- V36V (p.Val36Val), rs1555811725, gnomAD 17-68515507-G-T, CADD 20.70
- Q37* (p.Gln37Ter), cosmic curated COSV62236, Ensembl rs281864781
- Q37E (p.Gln37Glu), Ensembl rs281864781
- Q37H (p.Gln37His), rs750036578, ClinGen CA400751990, ClinVar RCV003516243, Uncertain significance, Carney complex, type 1
- Q37L (p.Gln37Leu), rs2143151932, ClinGen CA400751988, ClinVar RCV002428890, ClinVar RCV003626795, CADD 23.60, PolyPhen-2 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- Q37P (p.Gln37Pro), rs2143151932, ClinGen CA400751986, ClinVar RCV001883158, Ensembl rs2143151932, CADD 28.20, PolyPhen-2 0.74, Uncertain significance, Carney complex, type 1
- Q37R (p.Gln37Arg), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10067, Variant assessed as somatic; moderate impact.
- Q37Q (p.Gln37Gln), rs750036578, gnomAD 17-68515510-G-A, CADD 20.40
- L38S (p.Leu38Ser), cosmic curated COSV62235
- L38L (p.Leu38Leu), gnomAD 17-68515513-G-A, CADD 18.70
- C39F (p.Cys39Phe), rs2143152025, ClinGen CA400752002, ClinVar RCV001894207, ClinVar RCV003375378, AlphaMissense 1.00, MetaLR 0.68, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- C39Y (p.Cys39Tyr), rs2143152025, ClinGen CA400752001, ClinVar RCV002745280, Ensembl rs2143152025, AlphaMissense 1.00, MetaLR 0.68, Uncertain significance, Carney complex, type 1
- C39C (p.Cys39Cys), rs1423585756, gnomAD 17-68515516-C-T, CADD 18.60
- T40A (p.Thr40Ala), rs758013363, ClinGen CA8729160, ClinVar RCV001892567, ClinVar RCV002334802, CADD 23.00, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- T40I (p.Thr40Ile), Ensembl rs2085405205
- T40S (p.Thr40Ser), Ensembl rs2085405205, CADD 21.80, PolyPhen-2 0.10, Uncertain significance, Carney complex, type 1
- T40T (p.Thr40Thr), rs532516665, gnomAD 17-68515519-T-A, CADD 9.93
- A41D (p.Ala41Asp), rs1460961845, ClinGen CA400752016, ClinVar RCV001239978, ClinVar RCV004659438, CADD 17.60, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- A41T (p.Ala41Thr), rs1356757839, ClinGen CA400752011, ClinVar RCV000645597, ClinVar RCV001010406, CADD 20.30, PolyPhen-2 0.00, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- A41V (p.Ala41Val), rs1460961845, ClinGen CA400752015, ClinVar RCV004516143, TOPMed rs1460961845, CADD 18.70, PolyPhen-2 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A41A (p.Ala41Ala), rs1307987878, gnomAD 17-68515522-T-G, CADD 2.83
- R42* (p.Arg42Ter), rs281864782, ClinGen CA344422, NCI-TCGA Cosmic COSV6223, cosmic curated COSV62235, CADD 35.00, Pathogenic
- R42G (p.Arg42Gly), rs281864782, ClinGen CA8729161, ClinVar RCV002029118, ExAC rs281864782, CADD 23.60, PolyPhen-2 0.56, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- R42L (p.Arg42Leu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10067, Variant assessed as somatic; moderate impact.
- R42Q (p.Arg42Gln), rs746486900, ClinGen CA8729162, ClinVar RCV000818686, ClinVar RCV002427034, CADD 21.90, PolyPhen-2 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1; not provided
- R42R (p.Arg42Arg), gnomAD 17-68515525-A-C, CADD 3.07
- P43H (p.Pro43His), rs2143152627, ClinGen CA400752022, ClinVar RCV003296680, Ensembl rs2143152627, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome
- P43L (p.Pro43Leu), Ensembl rs2143152627, Uncertain significance
- P43S (p.Pro43Ser), rs1568688352, ClinGen CA400752021, cosmic curated COSV10743, ClinVar RCV001038621, CADD 25.10, PolyPhen-2 1.00, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- P43T (p.Pro43Thr), Ensembl rs1568688352, Uncertain significance
- E44D (p.Glu44Asp), rs145590804, ClinGen CA400752031, ClinVar RCV004516144, NCI-TCGA TCGA novel, Uncertain significance, Hereditary cancer-predisposing syndrome
- E44G (p.Glu44Gly), rs2085406021, ClinGen CA400752028, ClinVar RCV003627509, Ensembl rs2085406021, CADD 25.50, PolyPhen-2 0.28, Uncertain significance, Carney complex, type 1
- E44A (p.Glu44Ala), gnomAD 17-68515530-A-C, CADD 23.40, PolyPhen-2 0.02
- E44E (p.Glu44Glu), rs145590804, gnomAD 17-68515531-G-A, CADD 19.40
- R45D (p.Arg45Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R45K (p.Arg45Lys), rs2143152864, ClinGen CA400752035, ClinVar RCV002387917, ClinVar RCV003120992, AlphaMissense 0.11, MetaLR 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- R45T (p.Arg45Thr), cosmic curated COSV62235
- P46H (p.Pro46His), rs2085406263, ClinGen CA400752043, ClinVar RCV001203778, ClinVar RCV002379772, CADD 26.90, PolyPhen-2 1.00, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- P46R (p.Pro46Arg), Ensembl rs2085406263, Uncertain significance
- P46S (p.Pro46Ser), cosmic curated COSV62236
- P46P (p.Pro46Pro), gnomAD 17-68515537-C-G, CADD 17.40
- M47I (p.Met47Ile), Ensembl rs2143153168
- M47K (p.Met47Lys), rs2085406538, ClinGen CA400752048, ClinVar RCV003216337, AlphaMissense 0.33, MetaLR 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome
- M47L (p.Met47Leu), rs548529083, ClinGen CA400752047, ClinVar RCV001305431, TOPMed rs548529083, AlphaMissense 0.15, MetaLR 0.17, Uncertain significance, Carney complex, type 1
- M47T (p.Met47Thr), rs2085406538, ClinGen CA400752049, ClinVar RCV003165332, TOPMed rs2085406538, AlphaMissense 0.33, MetaLR 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome
- M47V (p.Met47Val), rs548529083, ClinGen CA293327657, ClinVar RCV001011385, ClinVar RCV001049581, AlphaMissense 0.15, MetaLR 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Carney complex, type 1
- A48D (p.Ala48Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A48T (p.Ala48Thr), rs2085406625, ClinGen CA400752055, NCI-TCGA Cosmic COSV6223, cosmic curated COSV62235, CADD 22.70, PolyPhen-2 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- A48A (p.Ala48Ala), rs1600462539, gnomAD 17-68515543-A-G, CADD 5.58
- F49L (p.Phe49Leu), cosmic curated COSV62235
- L50F (p.Leu50Phe), gnomAD rs1214905938, CADD 24.00, PolyPhen-2 0.17
- L50I (p.Leu50Ile), gnomAD rs1214905938
- L50L (p.Leu50Leu), rs2085406884, gnomAD 17-68515549-C-T, CADD 16.80
- R51G (p.Arg51Gly), rs967277610, ClinGen CA293327658, ClinVar RCV000695293, ClinVar RCV001011959, CADD 23.80, PolyPhen-2 0.67, Uncertain significance, Carney complex, type 1; Hereditary cancer-predisposing syndrome
- R51M (p.Arg51Met), cosmic curated COSV10067
- R51R (p.Arg51Arg), gnomAD 17-68515550-A-C, CADD 16.00
- R51K (p.Arg51Lys), gnomAD 17-68515551-G-A, CADD 23.20, PolyPhen-2 0.05
- E52G (p.Glu52Gly), rs748547646, ClinGen CA8729165, ClinVar RCV000793734, ExAC rs748547646, CADD 31.00, PolyPhen-2 0.47, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- E52K (p.Glu52Lys), rs2143153410, ClinGen CA400752080, ClinVar RCV001361973, ClinVar RCV002404854, CADD 24.10, PolyPhen-2 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Carney complex, type 1
- E52D (p.Glu52Asp), gnomAD 17-68515555-A-C, CADD 7.18, PolyPhen-2 0.02
- E52E (p.Glu52Glu), rs141432364, gnomAD 17-68515555-A-G, CADD 7.47
Public PRKAR1A analysis runs
- PRKAR1A analysis run — PRKAR1A (875 variants) — completed 2026-08-20