FBN1 (Fibrillin-1) variants and mutations
FBN1 (also known as Fibrillin-1) is a human protein-coding gene encoding a fibrillin-1 protein. Its fibrillin-1 microfibrils provide mechanical support to elastic tissues and regulate local availability of growth factors such as TGF-beta. Pathogenic variants cause Marfan syndrome and related fibrillinopathies affecting the aorta, skeleton, eyes, skin, and lungs. This analysis covers 5,411 FBN1 variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes Marfan syndrome, ectopia lentis 1, isolated, autosomal dominant, and Acromicric dysplasia. Example FBN1 variants include M1I, M1L, and M1R.
Variant analysis overview
- Gene: FBN1
- Protein: Fibrillin-1
- UniProt accession: P35555
- Organism: Homo sapiens
- Variants analyzed: 5411
- Variant scope: all variants
- Completed: 2026-09-18
Variant and mutation evidence
- Variant composition: 5,453 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 134 synonymous variants; 87 missense variants; 2 in-frame deletions; 4 stop-gained variants; 5 frameshift variants; 4 splice-region variants; 1 substitution
- Prediction scores: 3,925 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Marfan syndrome, ectopia lentis 1, isolated, autosomal dominant, Acromicric dysplasia, geleophysic dysplasia 2, stiff skin syndrome, progeroid and marfanoid aspect-lipodystrophy syndrome, Weill-Marchesani syndrome 2, dominant, MASS syndrome, aortic aneurysm, familial thoracic aortic aneurysm and aortic dissection, isolated ectopia lentis, thoracic aortic aneurysm.
Protein structure and variant hotspots
- Protein features: 56 domains; 44 post-translational modification sites.
- Structural context: 4,499 variants have structural context.
- PTM context: 64 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Diseases linked to FBN1
- Familial thoracic aortic aneurysm and aortic dissection genes and variants
- Marfan syndrome genes and variants
- Perrault syndrome genes and variants
- Connective tissue disease genes and variants
- Familial aortopathy genes and variants
- Isolated thoracic aortic aneurysm genes and variants
- Marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections genes and variants
- Ectopia lentis 1, isolated, autosomal dominant genes and variants
- Acromicric dysplasia genes and variants
- Geleophysic dysplasia genes and variants
- MASS syndrome genes and variants
- Weill-Marchesani syndrome 2, dominant genes and variants
Notable FBN1 variants
Examples include M1I, M1L, M1R, M1T, M1V, R2G, R3*, R3P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs886039072, ClinGen CA10587866, ClinVar RCV001256945, ClinVar RCV002311091, MetaLR 0.50, MetaSVM -0.00, Pathogenic, Marfan syndrome
- M1L (p.Met1Leu), rs730880097, ClinGen CA392454063, ClinVar RCV000700179, ClinVar RCV005831656, MetaLR 0.44, MetaSVM -0.23, Pathogenic
- M1R (p.Met1Arg), rs886041536, ClinGen CA10603351, ClinVar RCV000362200, ClinVar RCV002519049, MetaLR 0.53, MetaSVM 0.12, Pathogenic
- M1T (p.Met1Thr), rs886041536, ClinGen CA392454060, ClinVar RCV000663593, ClinVar RCV004788083, MetaLR 0.53, MetaSVM 0.12, Pathogenic
- M1V (p.Met1Val), rs730880097, ClinGen CA012702, ClinVar RCV000157222, ClinVar RCV002415683, MetaLR 0.44, MetaSVM -0.23, Pathogenic
- R2G (p.Arg2Gly), rs1597652545, ClinGen CA392454048, ClinVar RCV001000800, ClinVar RCV002337057, AlphaMissense 0.09, MetaLR 0.30, Uncertain significance
- R3* (p.Arg3Ter), rs886038797, ClinGen CA10587869, cosmic curated COSV57323, ClinVar RCV000246054, Pathogenic
- R3P (p.Arg3Pro), rs149929989, ClinGen CA060335, ClinVar RCV000773470, ClinVar RCV001338759, REVEL 0.07, CADD 22.70, Likely benign
- R3Q (p.Arg3Gln), rs149929989, ClinGen CA392454032, ClinVar RCV001998926, ESP rs149929989, REVEL 0.03, CADD 22.00, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- G4R (p.Gly4Arg), rs1890263469, ClinGen CA392454025, ClinVar RCV001194178, ClinVar RCV005225313, AlphaMissense 0.15, MetaLR 0.32, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome; not sp
- G4W (p.Gly4Trp), rs1890263469, ClinGen CA392454023, ClinVar RCV001524673, ClinVar RCV005213535, AlphaMissense 0.15, MetaLR 0.32, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- R5C (p.Arg5Cys), rs759323371, ClinGen CA044582, NCI-TCGA Cosmic COSV5732, cosmic curated COSV57326, REVEL 0.12, CADD 21.90, Conflicting interpretations, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R5H (p.Arg5His), rs1305871580, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, TOPMed rs1305871580, REVEL 0.05, CADD 22.80, Variant assessed as somatic; moderate impact.
- L6P (p.Leu6Pro), ExAC rs774145378, gnomAD rs774145378, REVEL 0.45, CADD 23.80
- L6V (p.Leu6Val), TOPMed rs1890263193
- E8D (p.Glu8Asp), rs2505822356, ClinGen CA392453968, ClinVar RCV004011749, Uncertain significance, Marfan syndrome
- A10V (p.Ala10Val), gnomAD rs1890262969, REVEL 0.15, CADD 17.20
- L11Q (p.Leu11Gln), rs1555407429, ClinGen CA392453932, ClinVar RCV000537232, ClinVar RCV000663626, AlphaMissense 0.51, MetaLR 0.57, Likely pathogenic
- L11R (p.Leu11Arg), rs1555407429, ClinGen CA392453927, ClinVar RCV000663627, ClinVar RCV001855413, AlphaMissense 0.51, MetaLR 0.57, Pathogenic
- L11V (p.Leu11Val), rs762468661, ClinGen CA050021, ClinVar RCV003528092, ClinVar RCV003779314, REVEL 0.19, CADD 23.80, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome; not sp
- G12* (p.Gly12Ter), rs2505822301, ClinGen CA392453922, ClinVar RCV003805603, Pathogenic
- F13C (p.Phe13Cys), rs773614956, ClinGen CA051680, ClinVar RCV001117420, ClinVar RCV001117421, REVEL 0.41, CADD 26.00, Benign
- T14I (p.Thr14Ile), TOPMed rs1357901401, REVEL 0.24, CADD 22.50, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- T14N (p.Thr14Asn), rs2505822290, ClinGen CA2580089588, ClinVar RCV003027265, Pathogenic
- V15G (p.Val15Gly), rs2140787791, ClinGen CA392453866, ClinVar RCV002246085, Ensembl rs2140787791, AlphaMissense 0.14, MetaLR 0.47, Uncertain significance, Marfan syndrome
- V15L (p.Val15Leu), rs1890262474, ClinGen CA392453881, ClinVar RCV004013991, REVEL 0.20, CADD 25.50, Uncertain significance, Marfan syndrome
- V15M (p.Val15Met), rs1890262474, ClinGen CA392453883, ClinVar RCV001225599, Ensembl rs1890262474, AlphaMissense 0.15, MetaLR 0.46, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- L16F (p.Leu16Phe), rs982368209, ClinGen CA270085545, ClinVar RCV001524466, ClinVar RCV001762715, REVEL 0.29, CADD 22.70, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- L16H (p.Leu16His), rs1555407424, ClinGen CA392453854, ClinVar RCV000663749, Ensembl rs1555407424, AlphaMissense 0.41, MetaLR 0.47, Likely pathogenic
- L16I (p.Leu16Ile), TOPMed rs982368209, gnomAD rs982368209, Uncertain significance
- L16P (p.Leu16Pro), rs1555407424, ClinGen CA392453853, ClinVar RCV003339221, ClinVar RCV005051289, AlphaMissense 0.41, MetaLR 0.47, Likely pathogenic, Familial thoracic aortic aneurysm and aortic dissection
- L16R (p.Leu16Arg), rs1555407424, ClinGen CA392453850, ClinVar RCV000588741, Ensembl rs1555407424, AlphaMissense 0.41, MetaLR 0.47, Likely pathogenic
- L16V (p.Leu16Val), rs982368209, ClinGen CA392453861, ClinVar RCV000584909, TOPMed rs982368209, AlphaMissense 0.06, MetaLR 0.39, Uncertain significance
- L17S (p.Leu17Ser), rs794728201, ClinGen CA015646, ClinVar RCV000181478, ClinVar RCV001351547, AlphaMissense 0.17, MetaLR 0.31, Uncertain significance
- A18G (p.Ala18Gly), ExAC rs770295085, TOPMed rs770295085, gnomAD rs770295085, REVEL 0.08, CADD 23.50, Uncertain significance
- A18P (p.Ala18Pro), rs1890262148, ClinGen CA392453831, ClinVar RCV001066526, ClinVar RCV005232103, AlphaMissense 0.32, MetaLR 0.28, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome; not pr
- A18V (p.Ala18Val), rs770295085, ClinGen CA270085538, ClinVar RCV003230879, ExAC rs770295085, REVEL 0.14, CADD 23.10, Uncertain significance, not specified
- S19F (p.Ser19Phe), rs193922218, ClinGen CA015969, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, REVEL 0.38, CADD 26.10, Likely pathogenic
- Y20* (p.Tyr20Ter), rs1057524735, ClinGen CA16607819, ClinVar RCV000420981, Ensembl rs1057524735, Likely pathogenic, in MFS
- Y20C (p.Tyr20Cys), rs201309310, ClinGen CA016208, ClinVar RCV000148501, ClinVar RCV000181402, REVEL 0.37, CADD 23.80, Likely benign, in MFS
- T21A (p.Thr21Ala), ExAC rs777027225, gnomAD rs777027225, REVEL 0.28, CADD 19.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- T21M (p.Thr21Met), rs1489806847, ClinGen CA392453797, ClinVar RCV001180957, ClinVar RCV001194175, REVEL 0.36, CADD 23.20, Conflicting interpretations, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not sp
- S22G (p.Ser22Gly), rs2140787724, ClinGen CA392453796, ClinVar RCV003237508, Ensembl rs2140787724, AlphaMissense 0.07, MetaLR 0.33, Uncertain significance, not provided
- S22R (p.Ser22Arg), rs1555407420, ClinGen CA392453783, ClinVar RCV000586748, Ensembl rs1555407420, AlphaMissense 0.19, MetaLR 0.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- H23L (p.His23Leu), Ensembl rs2140787715, REVEL 0.30, CADD 22.60
- G24A (p.Gly24Ala), rs768993489, ClinGen CA058005, ClinVar RCV001365363, ClinVar RCV006548216, REVEL 0.08, CADD 21.50, Conflicting interpretations, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- A25S (p.Ala25Ser), rs2505822123, ClinGen CA392453751, ClinVar RCV003801985, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- D26H (p.Asp26His), rs146267697, ClinGen CA059038, ClinVar RCV001183094, ClinVar RCV001315149, REVEL 0.16, CADD 23.20, Conflicting interpretations, not specified; Marfan syndrome; Familial thoracic aortic aneurysm and aortic dis
- A27T (p.Ala27Thr), rs25397, ClinGen CA017499, ClinVar RCV000150707, ClinVar RCV000246481, REVEL 0.10, CADD 12.40, Benign
- N28D (p.Asn28Asp), rs1555407418, ClinGen CA392453711, ClinVar RCV000590605, ClinVar RCV001311861, AlphaMissense 0.06, MetaLR 0.17, Uncertain significance
- N28S (p.Asn28Ser), rs193922245, ClinGen CA017720, ClinVar RCV000181490, ClinVar RCV000231311, REVEL 0.06, CADD 19.80, Likely benign
- L29F (p.Leu29Phe), rs2505822084, ClinGen CA392453688, ClinVar RCV003809094, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- E30* (p.Glu30Ter), rs2505822076, ClinGen CA392453684, ClinVar RCV002376063, Pathogenic
- E30D (p.Glu30Asp), rs778831047, ClinGen CA060356, ClinVar RCV000586371, ClinVar RCV003767335, REVEL 0.17, CADD 20.70, Likely benign
- A31T (p.Ala31Thr), rs371130701, ClinGen CA060367, ClinVar RCV001115964, ClinVar RCV001115965, REVEL 0.15, CADD 21.30, Benign
- G32E (p.Gly32Glu), rs2140787667, ClinGen CA392453661, ClinVar RCV001771179, ClinVar RCV004009025, AlphaMissense 0.08, MetaLR 0.27, Uncertain significance, not provided; Marfan syndrome
- N33S (p.Asn33Ser), rs2140787661, ClinGen CA392453654, ClinVar RCV002023627, Ensembl rs2140787661, REVEL 0.10, CADD 17.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- V34A (p.Val34Ala), rs1890260465, ClinGen CA392453646, ClinVar RCV001189595, Ensembl rs1890260465, AlphaMissense 0.07, MetaLR 0.20, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- V34L (p.Val34Leu), gnomAD rs1365346856, REVEL 0.10, CADD 17.90, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- V34M (p.Val34Met), rs1365346856, ClinGen CA392453650, ClinVar RCV003528091, gnomAD rs1365346856, REVEL 0.13, CADD 21.40, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K35R (p.Lys35Arg), 1000Genomes rs554167248, ExAC rs554167248, gnomAD rs554167248, REVEL 0.26, CADD 25.30
- T37N (p.Thr37Asn), rs1890260193, ClinGen CA392453626, ClinVar RCV001182407, TOPMed rs1890260193, AlphaMissense 0.07, MetaLR 0.16, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- T37S (p.Thr37Ser), TOPMed rs1890260193, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R38* (p.Arg38Ter), rs1355716557, ClinGen CA392453622, ClinVar RCV002246088, Ensembl rs1355716557, AlphaMissense 0.34, MetaLR 0.19, Pathogenic
- R38G (p.Arg38Gly), rs1355716557, ClinGen CA392453623, NCI-TCGA Cosmic COSV5730, cosmic curated COSV57309, AlphaMissense 0.34, MetaLR 0.19, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- R38T (p.Arg38Thr), TOPMed rs1015040634
- A39D (p.Ala39Asp), rs2505821956, ClinGen CA392453611, ClinVar RCV004015471, Uncertain significance, Marfan syndrome
- A39G (p.Ala39Gly), rs2505821956, ClinGen CA392453612, ClinVar RCV004016775, Uncertain significance, Marfan syndrome
- A39P (p.Ala39Pro), UniProt VAR 075984, Pathogenic, found in a patient with Marfan-like syndrome
- A39T (p.Ala39Thr), rs2505821961, ClinGen CA392453617, ClinVar RCV003994867, Uncertain significance, not specified
- R41G (p.Arg41Gly), rs1158441291, ClinGen CA392453592, ClinVar RCV001176112, ClinVar RCV004000322, REVEL 0.29, CADD 25.20, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Marfan sy
- R41P (p.Arg41Pro), rs1890259872, ClinGen CA392453588, ClinVar RCV001870661, TOPMed rs1890259872, AlphaMissense 0.85, MetaLR 0.42, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R41W (p.Arg41Trp), cosmic curated COSV10035, TOPMed rs1158441291, gnomAD rs1158441291, REVEL 0.53, CADD 27.90, Uncertain significance
- A42P (p.Ala42Pro), rs377722423, ClinGen CA044063, ClinVar RCV000458251, ClinVar RCV000729437, REVEL 0.40, CADD 24.90, Likely benign
- A42S (p.Ala42Ser), ESP rs377722423, ExAC rs377722423, TOPMed rs377722423, gnomAD rs377722423, REVEL 0.27, CADD 24.00, Likely benign
- K43* (p.Lys43Ter), rs751270801, ClinGen CA392453566, ClinVar RCV001380300, ClinVar RCV001508395, AlphaMissense 0.96, MetaLR 0.32, Pathogenic
- K43E (p.Lys43Glu), rs751270801, ClinGen CA044153, ClinVar RCV001769371, ExAC rs751270801, REVEL 0.32, CADD 24.90, Uncertain significance, not provided
- K43T (p.Lys43Thr), rs766081333, ClinGen CA044201, ClinVar RCV001064440, ClinVar RCV004000141, REVEL 0.31, CADD 24.70, Uncertain significance
- R44G (p.Arg44Gly), gnomAD rs1341910595, REVEL 0.58, CADD 32.00
- R44K (p.Arg44Lys), rs1890259213, ClinGen CA392453546, ClinVar RCV001887224, ClinVar RCV004010798, REVEL 0.35, CADD 24.90, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- R44S (p.Arg44Ser), rs1890259134, ClinGen CA392453543, ClinVar RCV001189597, ClinVar RCV001863000, AlphaMissense 0.99, MetaLR 0.58, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R45G (p.Arg45Gly), rs1597652333, ClinGen CA392453540, ClinVar RCV000788324, ClinVar RCV003528232, REVEL 0.54, CADD 27.00, Uncertain significance
- G46A (p.Gly46Ala), Ensembl rs1064797198, Uncertain significance
- G46D (p.Gly46Asp), rs1064797198, ClinGen CA16621673, ClinVar RCV000487617, Ensembl rs1064797198, AlphaMissense 0.19, MetaLR 0.61, Uncertain significance
- G46S (p.Gly46Ser), rs1890259021, ClinGen CA392453529, ClinVar RCV001185396, Ensembl rs1890259021, REVEL 0.41, CADD 27.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G47C (p.Gly47Cys), rs762400500, ClinGen CA392453522, ClinVar RCV000550995, ExAC rs762400500, AlphaMissense 0.13, MetaLR 0.49, Likely benign
- G47D (p.Gly47Asp), rs2505821841, ClinGen CA392453518, ClinVar RCV004012998, ClinVar RCV006550980, REVEL 0.43, CADD 24.10, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- G47S (p.Gly47Ser), rs762400500, ClinGen CA012118, ClinVar RCV000414982, ClinVar RCV000533830, REVEL 0.34, CADD 23.80, Likely benign
- G48E (p.Gly48Glu), rs1317580009, ClinGen CA392453506, ClinVar RCV002710502, TOPMed rs1317580009, AlphaMissense 0.58, MetaLR 0.69, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- G49* (p.Gly49Ter), Ensembl rs111935434
- G49A (p.Gly49Ala), rs1382204819, ClinGen CA392453493, ClinVar RCV000820304, ClinVar RCV004822231, REVEL 0.28, CADD 26.90, Uncertain significance
- G49E (p.Gly49Glu), rs1382204819, ClinGen CA392453495, cosmic curated COSV10515, ClinVar RCV003528089, REVEL 0.31, CADD 27.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G49V (p.Gly49Val), rs1382204819, ClinGen CA392453492, ClinVar RCV004007905, AlphaMissense 0.53, MetaLR 0.48, Uncertain significance, Marfan syndrome
- H50L (p.His50Leu), rs886039132, ClinGen CA10587864, ClinVar RCV000589289, ClinVar RCV001185056, REVEL 0.28, CADD 21.00, Uncertain significance
- H50Q (p.His50Gln), rs1597652302, ClinGen CA392453478, ClinVar RCV000995353, Ensembl rs1597652302, AlphaMissense 0.14, MetaLR 0.24, Likely benign
- D51E (p.Asp51Glu), rs1057524406, ClinGen CA16607114, ClinVar RCV000442624, ClinVar RCV003766453, REVEL 0.43, CADD 23.90, Uncertain significance
- D51N (p.Asp51Asn), rs2140787467, ClinGen CA392453472, NCI-TCGA Cosmic COSV5731, cosmic curated COSV57311, REVEL 0.27, CADD 29.60, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- A52T (p.Ala52Thr), rs749989129, cosmic curated COSV11446, NCI-TCGA Cosmic COSV5731, ExAC rs749989129, REVEL 0.21, CADD 24.00, Likely benign, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- A52V (p.Ala52Val), rs2140787437, ClinGen CA2499223018, ClinVar RCV001559081, ClinVar RCV003771709, REVEL 0.28, CADD 23.90, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- K54Q (p.Lys54Gln), rs2505821721, ClinGen CA392453431, ClinVar RCV004012991, Uncertain significance, Marfan syndrome
- G55* (p.Gly55Ter), rs1566944812, ClinGen CA392453406, ClinVar RCV000756145, ClinVar RCV005831663, AlphaMissense 0.92, SIFT 0.00, Pathogenic, in MFS
- G55A (p.Gly55Ala), rs2140787387, ClinGen CA392453403, ClinVar RCV002403641, ClinVar RCV004796729, AlphaMissense 0.99, MetaLR 0.79, Conflicting interpretations, Progeroid and marfanoid aspect-lipodystrophy syndrome; MASS syndrome; Geleophysi
- G55E (p.Gly55Glu), rs2140787387, ClinGen CA392453404, ClinVar RCV001374824, ClinVar RCV002537626, AlphaMissense 0.99, MetaLR 0.79, Likely pathogenic, Isolated thoracic aortic aneurysm; Familial thoracic aortic aneurysm and aortic
- G55R (p.Gly55Arg), rs1566944812, ClinGen CA392453409, ClinVar RCV004528683, REVEL 0.81, CADD 33.00, Uncertain significance, FBN1-related disorder
- P56L (p.Pro56Leu), rs1262119022, ClinGen CA392448530, ClinVar RCV001524898, TOPMed rs1262119022, REVEL 0.80, CADD 29.40, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- N57D (p.Asn57Asp), rs2044669685, ClinGen CA392448528, ClinVar RCV001317674, UniProt VAR 075986, AlphaMissense 0.95, MetaLR 0.74, Pathogenic, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- N57H (p.Asn57His), rs2044669685, ClinGen CA392448527, ClinVar RCV002223465, ClinVar RCV004808233, REVEL 0.71, CADD 26.70, Conflicting interpretations, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- N57S (p.Asn57Ser), rs2044669666, ClinGen CA392448525, ClinVar RCV001176000, ClinVar RCV001202339, REVEL 0.59, CADD 25.90, Uncertain significance, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- V58I (p.Val58Ile), NCI-TCGA TCGA novel, TOPMed rs2044669648, REVEL 0.25, CADD 24.20, Variant assessed as somatic; moderate impact.
- C59* (p.Cys59Ter), rs2044669557, ClinGen CA392448509, ClinVar RCV001179813, Ensembl rs2044669557, Pathogenic
- C59F (p.Cys59Phe), rs1555405673, ClinGen CA392448511, ClinVar RCV000663490, Ensembl rs1555405673, AlphaMissense 1.00, MetaLR 0.85, Likely pathogenic
- C59R (p.Cys59Arg), rs2140737589, ClinGen CA392448513, ClinVar RCV001963233, Ensembl rs2140737589, AlphaMissense 1.00, MetaLR 0.80, Pathogenic, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- C59Y (p.Cys59Tyr), rs1555405673, ClinGen CA392448510, ClinVar RCV000770681, ClinVar RCV005213391, AlphaMissense 1.00, MetaLR 0.85, Likely pathogenic
- G60A (p.Gly60Ala), ESP rs139788702, ExAC rs139788702, gnomAD rs139788702, REVEL 0.50, CADD 27.00, Uncertain significance
- G60E (p.Gly60Glu), rs139788702, ClinGen CA392448504, ClinVar RCV004008231, AlphaMissense 0.89, MetaLR 0.65, Uncertain significance, Marfan syndrome
- G60V (p.Gly60Val), ESP rs139788702, ExAC rs139788702, gnomAD rs139788702, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- S61* (p.Ser61Ter), rs2505779274, ClinGen CA392448499, ClinVar RCV003187815, ClinVar RCV003779584, Pathogenic
- S61P (p.Ser61Pro), rs1166519673, ClinGen CA392448501, ClinVar RCV001185571, ClinVar RCV004008539, REVEL 0.69, CADD 29.10, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- R62C (p.Arg62Cys), rs25403, ClinGen CA012607, ClinVar RCV000035129, ClinVar RCV000493952, REVEL 0.73, CADD 32.00, Pathogenic, in MFS
- R62H (p.Arg62His), rs145942328, ClinGen CA012618, ClinVar RCV000035130, ClinVar RCV000755193, REVEL 0.60, CADD 24.80, Pathogenic, in MFS
- Y63* (p.Tyr63Ter), rs1597633183, ClinGen CA392448486, ClinVar RCV000984035, Ensembl rs1597633183, Pathogenic, in ECTOL1
- Y63C (p.Tyr63Cys), rs1303389437, ClinGen CA392448489, ClinVar RCV000659499, ClinVar RCV001756116, AlphaMissense 0.56, MetaLR 0.56, Pathogenic, in ECTOL1
- Y63H (p.Tyr63His), rs867020123, ClinGen CA270060849, ClinVar RCV004017014, Ensembl rs867020123, AlphaMissense 0.26, MetaLR 0.44, Uncertain significance, Marfan syndrome
- A65T (p.Ala65Thr), gnomAD rs1467327594
- Y66* (p.Tyr66Ter), rs2044669179, ClinGen CA392448455, ClinVar RCV001813120, Ensembl rs2044669179, Pathogenic
- Y66C (p.Tyr66Cys), rs774371494, ClinGen CA392448458, ClinVar RCV000663510, ExAC rs774371494, AlphaMissense 0.14, MetaLR 0.63, Likely pathogenic
- Y66F (p.Tyr66Phe), rs774371494, ClinGen CA046551, ClinVar RCV003789273, ExAC rs774371494, REVEL 0.24, CADD 26.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- C67F (p.Cys67Phe), rs2044669166, ClinGen CA392448442, ClinVar RCV001225352, ClinVar RCV001812259, AlphaMissense 1.00, MetaLR 0.89, Pathogenic/Likely pathogenic, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- C67R (p.Cys67Arg), rs2140737496, ClinGen CA392448448, ClinVar RCV001917113, ClinVar RCV002422956, AlphaMissense 1.00, MetaLR 0.86, Likely pathogenic, Marfan syndrome
- C68F (p.Cys68Phe), rs1597633163, ClinGen CA392448429, ClinVar RCV001044191, Ensembl rs1597633163, AlphaMissense 1.00, MetaLR 0.72, Pathogenic, in ECTOL1
- C68L (p.Cys68Leu), rs2505779226, ClinGen CA2580089589, ClinVar RCV002811517, Pathogenic, in ECTOL1
- C68R (p.Cys68Arg), rs113604459, ClinGen CA270060842, ClinVar RCV000984036, Ensembl rs113604459, AlphaMissense 1.00, MetaLR 0.63, Likely pathogenic, in ECTOL1
- C68S (p.Cys68Ser), rs113604459, ClinGen CA392448434, ClinVar RCV000620921, UniProt VAR 075988, AlphaMissense 1.00, MetaLR 0.63, Pathogenic, in ECTOL1
- C68Y (p.Cys68Tyr), rs1597633163, ClinGen CA392448432, ClinVar RCV000804019, ClinVar RCV001258095, AlphaMissense 1.00, MetaLR 0.72, Pathogenic, in ECTOL1
- G70R (p.Gly70Arg), rs2044669023, ClinGen CA392448406, ClinVar RCV001054168, ClinVar RCV001290544, AlphaMissense 1.00, MetaLR 0.89, Likely pathogenic
- G70V (p.Gly70Val), rs2505779180, ClinGen CA392448397, ClinVar RCV002424179, ClinVar RCV003101054, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- W71* (p.Trp71Ter), rs2505779155, ClinGen CA392448366, ClinVar RCV003112313, Pathogenic
- W71G (p.Trp71Gly), rs1555405658, ClinGen CA392448386, ClinVar RCV001963595, Ensembl rs1555405658, AlphaMissense 1.00, MetaLR 0.81, Likely pathogenic, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- W71R (p.Trp71Arg), rs1555405658, ClinGen CA392448391, ClinVar RCV000663519, ClinVar RCV003767928, AlphaMissense 1.00, MetaLR 0.81, Pathogenic
- W71S (p.Trp71Ser), rs794728289, ClinGen CA012802, ClinVar RCV000181640, Ensembl rs794728289, AlphaMissense 1.00, MetaLR 0.84, Pathogenic
- T73I (p.Thr73Ile), rs2044668949, ClinGen CA392448320, ClinVar RCV001183796, Ensembl rs2044668949, AlphaMissense 0.90, MetaLR 0.70, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- P75R (p.Pro75Arg), rs1555405654, ClinGen CA392448272, ClinVar RCV000659500, ClinVar RCV004807076, AlphaMissense 0.65, MetaLR 0.46, Uncertain significance
- P75S (p.Pro75Ser), rs886051252, ClinGen CA10642094, ClinVar RCV000265294, ClinVar RCV000300622, REVEL 0.28, CADD 23.70, Likely benign
- G76R (p.Gly76Arg), Ensembl rs2044668857, REVEL 0.76, CADD 27.50
- G77R (p.Gly77Arg), rs794728290, ClinGen CA012938, NCI-TCGA Cosmic COSV5732, ClinVar RCV000181641, AlphaMissense 0.97, MetaLR 0.71, Likely pathogenic
- Q79L (p.Gln79Leu), TOPMed rs1338775496, REVEL 0.65, CADD 25.40, Uncertain significance
- Q79R (p.Gln79Arg), TOPMed rs1338775496, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection
- C80G (p.Cys80Gly), rs111764111, ClinGen CA392448179, ClinVar RCV000663534, UniProt VAR 065981, AlphaMissense 1.00, MetaLR 0.85, Pathogenic, in MFS
- C80R (p.Cys80Arg), rs111764111, ClinGen CA270060796, ClinVar RCV001240636, ClinVar RCV006372351, AlphaMissense 1.00, MetaLR 0.85, Pathogenic/Likely pathogenic, Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Diss
- C80Y (p.Cys80Tyr), rs397515767, ClinGen CA012984, ClinVar RCV000035136, ClinVar RCV001852706, AlphaMissense 1.00, MetaLR 0.86, Pathogenic, in MFS
- V82I (p.Val82Ile), rs148007052, ClinGen CA270060787, ClinVar RCV003796541, ClinVar RCV004006038, REVEL 0.32, CADD 23.90, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- P83H (p.Pro83His), gnomAD rs1206249804, REVEL 0.68, CADD 32.00, Uncertain significance
- P83L (p.Pro83Leu), rs1206249804, ClinGen CA392447206, ClinVar RCV001366224, gnomAD rs1206249804, AlphaMissense 1.00, MetaLR 0.76, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- P83S (p.Pro83Ser), rs1257434757, ClinGen CA392448107, ClinVar RCV002988401, TOPMed rs1257434757, REVEL 0.65, CADD 33.00, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- I84V (p.Ile84Val), TOPMed rs921420972, gnomAD rs921420972, REVEL 0.39, CADD 23.40, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- C85* (p.Cys85Ter), rs1555405536, ClinGen CA392447170, ClinVar RCV000663555, Ensembl rs1555405536, Pathogenic
- C85Y (p.Cys85Tyr), rs2505775858, ClinGen CA392447177, ClinVar RCV003783680, ClinVar RCV005230566, Pathogenic, not provided; Familial thoracic aortic aneurysm and aortic dissection; Marfan sy
- R86G (p.Arg86Gly), rs2505775850, ClinGen CA2580089569, ClinVar RCV002889789, Pathogenic
- R86Q (p.Arg86Gln), rs2044650738, ClinGen CA392447159, ClinVar RCV001990134, ClinVar RCV004010981, REVEL 0.53, CADD 31.00, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R86W (p.Arg86Trp), rs769979790, ClinGen CA048069, ClinVar RCV004011982, ExAC rs769979790, REVEL 0.67, CADD 29.20, Uncertain significance, Marfan syndrome
- H87N (p.His87Asn), ExAC rs747008489, TOPMed rs747008489, gnomAD rs747008489, REVEL 0.29, CADD 19.20
- H87R (p.His87Arg), rs1060501080, ClinGen CA16614458, ClinVar RCV000470077, ClinVar RCV006550116, AlphaMissense 0.28, MetaLR 0.25, Uncertain significance
- S88C (p.Ser88Cys), Ensembl rs111399779
- S88F (p.Ser88Phe), Ensembl rs111399779
- C89F (p.Cys89Phe), rs112660651, ClinGen CA270059115, ClinVar RCV001215009, ClinVar RCV001537030, AlphaMissense 1.00, MetaLR 0.79, Pathogenic, not provided; Familial thoracic aortic aneurysm and aortic dissection; Marfan sy
- C89R (p.Cys89Arg), rs1555405533, ClinGen CA392447117, ClinVar RCV000663565, Ensembl rs1555405533, AlphaMissense 1.00, MetaLR 0.77, Likely pathogenic, in MFS
- C89S (p.Cys89Ser), rs112660651, ClinGen CA013283, ClinVar RCV000029715, Ensembl rs112660651, AlphaMissense 1.00, MetaLR 0.79, Pathogenic, in MFS
- C89Y (p.Cys89Tyr), rs112660651, ClinGen CA013275, ClinVar RCV000181643, ClinVar RCV000539344, AlphaMissense 1.00, MetaLR 0.79, Pathogenic, in MFS
- G90A (p.Gly90Ala), rs2140734033, ClinGen CA392447075, ClinVar RCV001805632, Ensembl rs2140734033, REVEL 0.52, CADD 25.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G90R (p.Gly90Arg), rs2505775795, ClinGen CA392447093, ClinVar RCV003528087, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G92R (p.Gly92Arg), rs2140734026, ClinGen CA392447059, ClinVar RCV002034611, ClinVar RCV002246024, AlphaMissense 1.00, MetaLR 0.85, Likely pathogenic, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- F93C (p.Phe93Cys), Ensembl rs112271157
- C94T (p.Cys94Thr), NCI-TCGA Cosmic COSV5731, cosmic curated COSV57310, Variant assessed as somatic; moderate impact.
- C94F (p.Cys94Phe), Ensembl rs730880098, Pathogenic
- C94Y (p.Cys94Tyr), rs730880098, ClinGen CA392447037, ClinVar RCV003783679, ClinVar RCV006605412, AlphaMissense 1.00, MetaLR 0.87, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- S95* (p.Ser95Ter), rs922684362, ClinGen CA392447031, ClinVar RCV002272603, ClinVar RCV005227561, AlphaMissense 0.98, MetaLR 0.71, Pathogenic
- S95L (p.Ser95Leu), rs922684362, ClinGen CA270059090, NCI-TCGA Cosmic COSV1003, ClinVar RCV001187889, REVEL 0.51, CADD 29.20, Uncertain significance, not provided; Marfan syndrome; Familial thoracic aortic aneurysm and aortic diss
- S95W (p.Ser95Trp), rs922684362, ClinGen CA392447030, ClinVar RCV000859996, TOPMed rs922684362, AlphaMissense 0.98, MetaLR 0.71, Pathogenic
- R96T (p.Arg96Thr), rs794728291, ClinGen CA013493, ClinVar RCV000181644, ClinVar RCV000243821, REVEL 0.51, CADD 25.90, Likely pathogenic
- N98S (p.Asn98Ser), rs2505775716, ClinGen CA392447012, ClinVar RCV004010183, REVEL 0.47, CADD 25.60, Uncertain significance, Marfan syndrome
Public FBN1 analysis runs
- FBN1 analysis run — FBN1 (5,411 variants) — completed 2026-09-18
- FBN1 analysis run — FBN1 (5,677 variants) — completed 2026-08-10