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 5,677 FBN1 variants and mutations. Of these, 40% have pathogenic or likely pathogenic clinical classifications, 73% have computational variant effect predictions from REVEL and MutPred, and 37% have population-specific frequency data. 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: 5677
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 5,441 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 134 synonymous variants; 84 missense variants; 2 in-frame deletions; 4 stop-gained variants; 5 frameshift variants; 4 splice-region variants; 1 substitution
- Clinical classifications: 2,277 pathogenic or likely pathogenic; 439 benign or likely benign; 1,827 uncertain-significance; 3 conflicting; 362 other clinical labels.
- Computational signals: 615 REVEL high-risk; 1,547 MutPred high-risk.
- Variant classes: 5,095 missense; 134 synonymous; 446 truncating or splice.
- Prediction scores: 4,171 variants have prediction scores (73% of the analyzed set).
- Literature: 2 publications are represented in the literature summary.
Clinical, disease, and population context
- Clinical evidence: 131 records have expert-only or criteria-backed evidence.
- Clinical annotations: 4,908 variants have clinical annotations.
- Population evidence: 2,201 variants have population-frequency evidence.
- 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, a patient with Marfan-like syndrome, ECTOL1, GPHYSD2, a patient with Shprintzen-Goldberg craniosynostosis syndrome.
Protein structure and variant hotspots
- Protein features: 56 domains; 44 post-translational modification sites.
- Ancestry evidence: 2,094 variants have ancestry-specific frequency data.
- Structural context: 4,712 variants have structural context.
- PTM context: 68 variants overlap post-translational modification sites.
- gnomAD gene constraint: pLI 1.00 (highly intolerant of loss-of-function variation); LOEUF 0.08; missense Z-score 8.60.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable FBN1 variants
Examples include M1I, M1L, M1R, M1T, M1V, R2C, R2G, R3*. 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
- 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
- R2C (p.Arg2Cys), NCI-TCGA Cosmic COSV5731, cosmic curated COSV57312, REVEL 0.33, MetaLR 0.41, Variant assessed as somatic; moderate impact.
- 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, MetaLR 0.38, Likely benign
- R3Q (p.Arg3Gln), rs149929989, ClinGen CA392454032, ClinVar RCV001998926, ESP rs149929989, REVEL 0.03, MetaLR 0.37, 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, MetaLR 0.34, 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, MetaLR 0.30, Variant assessed as somatic; moderate impact.
- L6P (p.Leu6Pro), ExAC rs774145378, gnomAD rs774145378, REVEL 0.45, MetaLR 0.44
- L6V (p.Leu6Val), TOPMed rs1890263193
- E8D (p.Glu8Asp), rs2505822356, ClinGen CA392453968, ClinVar RCV004011749, Uncertain significance, Marfan syndrome
- A10T (p.Ala10Thr), NCI-TCGA Cosmic COSV5731, cosmic curated COSV57316, REVEL 0.14, MetaLR 0.27, Variant assessed as somatic; moderate impact.
- A10V (p.Ala10Val), gnomAD rs1890262969, REVEL 0.15, MetaLR 0.26
- 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, MetaLR 0.52, 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, MetaLR 0.37, Conflicting interpretations, Acromicric dysplasia; Familial thoracic aortic aneurysm and aortic dissection; M
- T14I (p.Thr14Ile), TOPMed rs1357901401, REVEL 0.24, MetaLR 0.41, 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, AlphaMissense 0.15, 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, AlphaMissense 0.06, 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, Uncertain significance
- 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, Uncertain significance
- 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, MetaLR 0.27, 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, MetaLR 0.26, Uncertain significance, not specified
- S19F (p.Ser19Phe), rs193922218, ClinGen CA015969, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, REVEL 0.38, MetaLR 0.48, 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, MetaLR 0.26, Likely benign, in MFS
- T21A (p.Thr21Ala), ExAC rs777027225, gnomAD rs777027225, REVEL 0.28, MetaLR 0.24, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- T21M (p.Thr21Met), rs1489806847, ClinGen CA392453797, ClinVar RCV001180957, ClinVar RCV001194175, REVEL 0.36, MetaLR 0.35, 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
- S22N (p.Ser22Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- 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, MetaLR 0.17
- G24A (p.Gly24Ala), rs768993489, ClinGen CA058005, ClinVar RCV001365363, ClinVar RCV006548216, REVEL 0.08, MetaLR 0.26, 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
- A25V (p.Ala25Val), NCI-TCGA Cosmic COSV5732, cosmic curated COSV57325, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- D26H (p.Asp26His), rs146267697, ClinGen CA059038, ClinVar RCV001183094, ClinVar RCV001315149, REVEL 0.16, MetaLR 0.36, 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, MetaLR 0.27, 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, MetaLR 0.21, 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, MetaLR 0.31, Likely benign
- A31T (p.Ala31Thr), rs371130701, ClinGen CA060367, ClinVar RCV001115964, ClinVar RCV001115965, REVEL 0.15, MetaLR 0.25, Benign
- A31V (p.Ala31Val), NCI-TCGA Cosmic COSV5731, cosmic curated COSV57310, REVEL 0.18, MetaLR 0.30, Variant assessed as somatic; moderate impact.
- 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, MetaLR 0.24, 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, MetaLR 0.20, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- V34M (p.Val34Met), rs1365346856, ClinGen CA392453650, ClinVar RCV003528091, gnomAD rs1365346856, REVEL 0.13, MetaLR 0.26, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K35R (p.Lys35Arg), 1000Genomes rs554167248, ExAC rs554167248, gnomAD rs554167248, REVEL 0.26, MetaLR 0.27
- E36K (p.Glu36Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, Variant assessed as somatic; moderate impact.
- 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
- R38K (p.Arg38Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- 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, MetaLR 0.39, 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, MetaLR 0.55, Uncertain significance
- A42P (p.Ala42Pro), rs377722423, ClinGen CA044063, ClinVar RCV000458251, ClinVar RCV000729437, REVEL 0.40, MetaLR 0.45, Likely benign
- A42S (p.Ala42Ser), ESP rs377722423, ExAC rs377722423, TOPMed rs377722423, gnomAD rs377722423, REVEL 0.27, MetaLR 0.38, 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, AlphaMissense 0.96, Uncertain significance, not provided
- K43T (p.Lys43Thr), rs766081333, ClinGen CA044201, ClinVar RCV001064440, ClinVar RCV004000141, REVEL 0.31, MetaLR 0.23, Uncertain significance
- R44G (p.Arg44Gly), gnomAD rs1341910595, REVEL 0.58, MetaLR 0.60
- R44I (p.Arg44Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R44K (p.Arg44Lys), rs1890259213, ClinGen CA392453546, ClinVar RCV001887224, ClinVar RCV004010798, REVEL 0.35, MetaLR 0.65, 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, MetaLR 0.64, 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, MetaLR 0.61, 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, MetaLR 0.62, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- G47S (p.Gly47Ser), rs762400500, ClinGen CA012118, ClinVar RCV000414982, ClinVar RCV000533830, REVEL 0.34, AlphaMissense 0.13, 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, AlphaMissense 0.53, Uncertain significance
- G49E (p.Gly49Glu), rs1382204819, ClinGen CA392453495, cosmic curated COSV10515, ClinVar RCV003528089, REVEL 0.31, AlphaMissense 0.53, 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, MetaLR 0.19, 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, MetaLR 0.38, Uncertain significance
- D51N (p.Asp51Asn), rs2140787467, ClinGen CA392453472, NCI-TCGA Cosmic COSV5731, cosmic curated COSV57311, REVEL 0.27, MetaLR 0.56, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- A52T (p.Ala52Thr), rs749989129, NCI-TCGA Cosmic COSV5731, ExAC rs749989129, gnomAD rs749989129, REVEL 0.21, MetaLR 0.37, Likely benign, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- A52V (p.Ala52Val), rs2140787437, ClinGen CA2499223018, ClinVar RCV001559081, ClinVar RCV003771709, REVEL 0.28, MetaLR 0.40, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- L53I (p.Leu53Ile), NCI-TCGA Cosmic COSV5732, cosmic curated COSV57323, REVEL 0.27, MetaLR 0.64, Variant assessed as somatic; moderate impact.
- 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, AlphaMissense 0.92, Uncertain significance, FBN1-related disorder
- P56H (p.Pro56His), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- P56L (p.Pro56Leu), rs1262119022, ClinGen CA392448530, ClinVar RCV001524898, TOPMed rs1262119022, REVEL 0.80, MetaLR 0.70, 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, AlphaMissense 0.95, 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, MetaLR 0.72, 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, MetaLR 0.66, 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, AlphaMissense 0.89
- 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, MetaLR 0.72, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- R62C (p.Arg62Cys), rs25403, ClinGen CA012607, ClinVar RCV000035129, ClinVar RCV000493952, REVEL 0.73, MetaLR 0.75, Pathogenic, in MFS
- R62H (p.Arg62His), rs145942328, ClinGen CA012618, ClinVar RCV000035130, ClinVar RCV000755193, REVEL 0.60, MetaLR 0.70, 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, AlphaMissense 0.14, 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
- G70A (p.Gly70Ala), NCI-TCGA Cosmic COSV5731, Variant assessed as somatic; moderate impact.
- 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, MetaLR 0.41, Likely benign
- G76R (p.Gly76Arg), Ensembl rs2044668857, REVEL 0.76, MetaLR 0.71
- 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, MetaLR 0.49
- 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, Familial thoracic aortic aneurysm and aortic dissection; Marfan syndrome
- C80Y (p.Cys80Tyr), rs397515767, ClinGen CA012984, ClinVar RCV000035136, ClinVar RCV001852706, AlphaMissense 1.00, MetaLR 0.86, Pathogenic, in MFS
- V82=, NCI-TCGA Cosmic COSV5732, Variant assessed as somatic; low impact.
- V82A (p.Val82Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V82I (p.Val82Ile), rs148007052, ClinGen CA270060787, ClinVar RCV003796541, ClinVar RCV004006038, REVEL 0.32, MetaLR 0.60, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection; not pr
- P83=, NCI-TCGA Cosmic COSV5732, Variant assessed as somatic; low impact.
- P83H (p.Pro83His), gnomAD rs1206249804, REVEL 0.68, AlphaMissense 1.00, 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, MetaLR 0.76, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- I84V (p.Ile84Val), TOPMed rs921420972, gnomAD rs921420972, REVEL 0.39, MetaLR 0.58, 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, MetaLR 0.65, Uncertain significance, Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection
- R86W (p.Arg86Trp), rs769979790, ClinGen CA048069, ClinVar RCV004011982, ExAC rs769979790, REVEL 0.67, MetaLR 0.69, Uncertain significance, Marfan syndrome
- H87N (p.His87Asn), ExAC rs747008489, TOPMed rs747008489, gnomAD rs747008489, REVEL 0.29, MetaLR 0.18
- H87R (p.His87Arg), rs1060501080, ClinGen CA16614458, ClinVar RCV000470077, ClinVar RCV006550116, AlphaMissense 0.28, MetaLR 0.25, Uncertain significance
- H87Y (p.His87Tyr), NCI-TCGA Cosmic COSV5732, Variant assessed as somatic; moderate impact.
- 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
Public FBN1 analysis runs
- FBN1 analysis run — FBN1 (5,677 variants) — completed 2026-08-10