ACTA2 (Actin, aortic smooth muscle) variants and mutations
ACTA2 (also known as Actin, aortic smooth muscle) is a human protein-coding gene encoding an actin, aortic smooth muscle protein. Its smooth-muscle actin filaments generate contractile force in arteries and visceral organs and help maintain vascular-wall structure. Pathogenic variants are an important cause of familial thoracic aortic aneurysm and dissection and can also produce occlusive vascular disease. This analysis covers 668 ACTA2 variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes aortic aneurysm, familial thoracic 6, multisystemic smooth muscle dysfunction syndrome, and Moyamoya disease 5. Example ACTA2 variants include M1I, M1V, and C2S.
Variant analysis overview
- Gene: ACTA2
- Protein: Actin, aortic smooth muscle
- UniProt accession: P62736
- Organism: Homo sapiens
- Variants analyzed: 668
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 433 unspecified-consequence records; 1 stop retained variant; 121 synonymous variants; 71 missense variants; 3 stop-gained variants; 23 frameshift variants; 5 splice-region variants; 1 in-frame insertions; 2 in-frame deletions; 7 substitution
- Prediction scores: 520 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: aortic aneurysm, familial thoracic 6, multisystemic smooth muscle dysfunction syndrome, Moyamoya disease 5, familial thoracic aortic aneurysm and aortic dissection, Moyamoya disease, thoracic aortic aneurysm, Rare disease with thoracic aortic aneurysm and aortic dissection, Rare genetic vascular disease, Abnormality of the cardiovascular system, lymphoid leukemia, B-cell chronic lymphocytic leukemia, Familial hemophagocytic lymphohistiocytosis.
Protein structure and variant hotspots
- Protein features: 6 post-translational modification sites.
- PTM context: 13 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable ACTA2 variants
Examples include M1I, M1V, C2S, C2Y, E3K, E5A, E5K, E5Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1182412944, ClinGen CA377513858, ClinVar RCV003074749, MetaLR 0.91, MetaSVM 1.03, Uncertain significance, Aortic aneurysm, familial thoracic 6
- M1V (p.Met1Val), rs794728019, ClinGen CA006856, ClinVar RCV000181012, ClinVar RCV005401354, MetaLR 0.89, MetaSVM 0.98, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- C2S (p.Cys2Ser), rs1846002030, ClinGen CA377513853, ClinVar RCV001236528, ClinVar RCV003166464, REVEL 0.53, CADD 23.30, Uncertain significance, Aortic aneurysm, familial thoracic 6; not provided; Familial thoracic aortic ane
- C2Y (p.Cys2Tyr), rs750805652, ExAC rs750805652, gnomAD rs750805652, REVEL 0.54, CADD 24.20, Variant assessed as somatic; moderate impact.
- E3K (p.Glu3Lys), NCI-TCGA Cosmic COSV5651, Variant assessed as somatic; moderate impact.
- E5A (p.Glu5Ala), rs1846001785, ClinGen CA377513830, ClinVar RCV001191959, Ensembl rs1846001785, AlphaMissense 0.21, MetaLR 0.87, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- E5K (p.Glu5Lys), rs886047453, ClinGen CA377513832, ClinVar RCV003528722, REVEL 0.71, CADD 23.90, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- E5Q (p.Glu5Gln), rs886047453, ClinGen CA10629419, NCI-TCGA Cosmic COSV5651, ClinVar RCV000271493, REVEL 0.68, CADD 24.80, Uncertain significance, not provided; Multisystemic smooth muscle dysfunction syndrome; Aortic aneurysm
- D6G (p.Asp6Gly), rs1064796603, ClinGen CA16619079, ClinVar RCV000487316, TOPMed rs1064796603, REVEL 0.70, CADD 26.70, Uncertain significance, not provided
- D6N (p.Asp6Asn), gnomAD rs1244752076, REVEL 0.49, CADD 23.50
- S7G (p.Ser7Gly), ExAC rs765607611, gnomAD rs765607611, REVEL 0.41, CADD 23.20, Uncertain significance, Aortic aneurysm, familial thoracic 6
- S7N (p.Ser7Asn), rs2494579025, ClinGen CA377513816, ClinVar RCV003870474, REVEL 0.35, CADD 21.90, Uncertain significance, Aortic aneurysm, familial thoracic 6
- A9P (p.Ala9Pro), gnomAD rs1451974556, REVEL 0.79, CADD 23.30
- C12* (p.Cys12Ter), rs1589400454, ClinGen CA377513780, ClinVar RCV003516767, Uncertain significance
- S16P (p.Ser16Pro), rs1554841990, ClinGen CA377513755, ClinVar RCV000645621, Ensembl rs1554841990, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Aortic aneurysm, familial thoracic 6
- C19R (p.Cys19Arg), rs2133273980, ClinGen CA377513737, ClinVar RCV001362509, Ensembl rs2133273980, AlphaMissense 1.00, MetaLR 0.94, Likely pathogenic, Aortic aneurysm, familial thoracic 6
- C19S (p.Cys19Ser), rs2494578654, ClinGen CA377513734, ClinVar RCV003518313, Uncertain significance, Aortic aneurysm, familial thoracic 6
- K20N (p.Lys20Asn), rs373232511, ClinGen CA377513724, ClinVar RCV002360163, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A21S (p.Ala21Ser), rs2494578519, ClinGen CA377513720, ClinVar RCV003341611, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G22S (p.Gly22Ser), rs756496192, ClinGen CA211328501, NCI-TCGA Cosmic COSV5651, ClinVar RCV001524016, REVEL 0.93, CADD 28.10, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Aortic aneurysm, famili
- F23I (p.Phe23Ile), rs1589400425, ClinGen CA377513711, ClinVar RCV001001351, Ensembl rs1589400425, AlphaMissense 0.98, MetaLR 0.93, Uncertain significance, not specified
- F23L (p.Phe23Leu), ExAC rs759122203, gnomAD rs759122203, REVEL 0.81, CADD 22.10
- G25R (p.Gly25Arg), rs1554841985, ClinGen CA377513698, ClinVar RCV000525618, Ensembl rs1554841985, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, Aortic aneurysm, familial thoracic 6
- D26E (p.Asp26Glu), rs141538225, ClinGen CA029465, ClinVar RCV000703601, ClinVar RCV001524997, REVEL 0.63, CADD 5.55, Uncertain significance, Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5; Aortic ane
- D26H (p.Asp26His), rs1438979811, ClinGen CA377513692, ClinVar RCV001191610, ClinVar RCV001228407, REVEL 0.94, AlphaMissense 1.00, Uncertain significance, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- D26N (p.Asp26Asn), rs1438979811, ClinGen CA377513691, ClinVar RCV004173737, AlphaMissense 1.00, MetaLR 0.95, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- D26Y (p.Asp26Tyr), NCI-TCGA Cosmic COSV5651, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- D27N (p.Asp27Asn), rs794728020, ClinGen CA007036, ClinVar RCV001799144, ClinVar RCV006557741, AlphaMissense 1.00, MetaLR 0.81, Conflicting interpretations, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- A28D (p.Ala28Asp), rs886038855, ClinGen CA377513675, ClinVar RCV004014803, AlphaMissense 0.99, MetaLR 0.86, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A28V (p.Ala28Val), rs886038855, ClinGen CA10587715, ClinVar RCV000694475, ClinVar RCV001179389, AlphaMissense 0.99, MetaLR 0.86, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- R30K (p.Arg30Lys), rs2494578139, ClinGen CA377513665, ClinVar RCV004011938, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- R30S (p.Arg30Ser), gnomAD rs1445850454, REVEL 0.75, CADD 23.70
- R30W (p.Arg30Trp), rs1564647905, ClinGen CA377513666, ClinVar RCV000690957, Ensembl rs1564647905, AlphaMissense 1.00, MetaLR 0.95, Uncertain significance, Aortic aneurysm, familial thoracic 6
- R30T (p.Arg30Thr), rs996293451, []
- R30L (p.Arg30Leu), rs903460339, []
- A31V (p.Ala31Val), rs2494578084, ClinGen CA377513655, ClinVar RCV002371527, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- S35Y (p.Ser35Tyr), rs1845999816, ClinGen CA377513630, ClinVar RCV001224008, Ensembl rs1845999816, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Aortic aneurysm, familial thoracic 6
- I36T (p.Ile36Thr), rs772919504, ClinGen CA026722, NCI-TCGA Cosmic COSV5651, ClinVar RCV000788973, REVEL 0.89, CADD 29.20, Uncertain significance, Aortic aneurysm, familial thoracic 6; not specified; not provided
- I36V (p.Ile36Val), rs1845999767, ClinGen CA377513627, ClinVar RCV001178201, TOPMed rs1845999767, REVEL 0.65, CADD 23.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- R39C (p.Arg39Cys), rs112901682, ClinGen CA006817, NCI-TCGA Cosmic COSV5651, ClinVar RCV000055647, REVEL 0.85, AlphaMissense 0.99, Pathogenic/Likely pathogenic, Thoracic aortic aneurysm or dissection; Aortic aneurysm, familial thoracic 6; Mu
- R39G (p.Arg39Gly), rs112901682, ClinGen CA006808, ClinVar RCV000645628, ClinVar RCV001812161, AlphaMissense 0.99, MetaLR 0.82, Pathogenic/Likely pathogenic, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- R39H (p.Arg39His), rs794728021, ClinGen CA006825, NCI-TCGA Cosmic COSV5651, ClinVar RCV000181015, AlphaMissense 0.89, MetaLR 0.84, Pathogenic/Likely pathogenic, not provided; Familial aortopathy; Familial thoracic aortic aneurysm and aortic
- R39S (p.Arg39Ser), rs112901682, ClinGen CA377513610, ClinVar RCV001377371, gnomAD rs112901682, AlphaMissense 0.99, MetaLR 0.82, Likely pathogenic, Aortic aneurysm, familial thoracic 6
- P40P (p.Pro40Pro), rs949028791, []
- H42Y (p.His42Tyr), rs2494577872, ClinGen CA377513592, ClinVar RCV003872210, REVEL 0.80, CADD 23.50, Uncertain significance, Aortic aneurysm, familial thoracic 6
- Q43* (p.Gln43Ter), TOPMed rs1845999368
- V45A (p.Val45Ala), rs1554841848, ClinGen CA377513557, ClinVar RCV000645620, Ensembl rs1554841848, AlphaMissense 0.94, MetaLR 0.90, Uncertain significance, Aortic aneurysm, familial thoracic 6
- V45G (p.Val45Gly), Ensembl rs1554841848, Uncertain significance
- M46I (p.Met46Ile), rs878854466, ClinGen CA10582774, ClinVar RCV000227796, Ensembl rs878854466, AlphaMissense 1.00, MetaLR 0.83, Pathogenic/Likely pathogenic, not provided; Aortic aneurysm, familial thoracic 6
- M46R (p.Met46Arg), rs1554841843, ClinGen CA377513550, ClinVar RCV000498466, Ensembl rs1554841843, AlphaMissense 1.00, MetaLR 0.87, Likely pathogenic, not provided
- M46V (p.Met46Val), rs2133270221, ClinGen CA377513554, ClinVar RCV001923663, Ensembl rs2133270221, REVEL 0.89, CADD 24.60, Likely pathogenic, Aortic aneurysm, familial thoracic 6
- V47L (p.Val47Leu), gnomAD rs1181233032, REVEL 0.77, CADD 23.90, Uncertain significance
- V47M (p.Val47Met), rs1181233032, ClinGen CA377513545, ClinVar RCV000722384, ClinVar RCV000815736, REVEL 0.80, CADD 26.90, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Aortic aneurysm, famili
- G48* (p.Gly48Ter), rs869025351, ClinGen CA352096, ClinVar RCV000208504, Ensembl rs869025351, Uncertain significance
- G48E (p.Gly48Glu), rs2494571084, ClinGen CA377513539, ClinVar RCV003338958, ClinVar RCV003517486, Uncertain significance, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- G48V (p.Gly48Val), rs2494571084, ClinGen CA377513537, ClinVar RCV002394340, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- M49K (p.Met49Lys), rs869025352, ClinGen CA351763, ClinVar RCV000208083, Ensembl rs869025352, AlphaMissense 0.99, MetaLR 0.85, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- M49T (p.Met49Thr), rs869025352, ClinGen CA377513533, ClinVar RCV002314193, ClinVar RCV002531810, AlphaMissense 0.99, MetaLR 0.85, Likely pathogenic, Familial aortopathy; Familial thoracic aortic aneurysm and aortic dissection; Ao
- M49V (p.Met49Val), rs397515325, ClinGen CA006843, ClinVar RCV000055648, Ensembl rs397515325, AlphaMissense 0.91, MetaLR 0.83, Pathogenic, Aortic aneurysm, familial thoracic 6
- G50R (p.Gly50Arg), rs2494571043, ClinGen CA377513529, ClinVar RCV003633430, REVEL 0.91, CADD 31.00, Uncertain significance, Aortic aneurysm, familial thoracic 6
- Q51L (p.Gln51Leu), Ensembl rs2133270145
- Q51P (p.Gln51Pro), rs2133270145, ClinGen CA377513518, ClinVar RCV002400835, REVEL 0.89, CADD 28.50, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K52E (p.Lys52Glu), rs1589399071, ClinGen CA377513514, ClinVar RCV000788481, ClinVar RCV001290138, AlphaMissense 1.00, MetaLR 0.90, Uncertain significance, Aortic aneurysm, familial thoracic 6; not provided
- V56M (p.Val56Met), rs1845970585, ClinGen CA377513483, ClinVar RCV003528720, gnomAD rs1845970585, REVEL 0.82, CADD 24.60, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G57R (p.Gly57Arg), rs1845970518, ClinGen CA377513476, ClinVar RCV001070817, Ensembl rs1845970518, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Aortic aneurysm, familial thoracic 6
- G57S (p.Gly57Ser), rs1845970518, ClinGen CA377513477, ClinVar RCV003887254, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, not provided
- G57V (p.Gly57Val), rs1564647168, ClinGen CA377513474, ClinVar RCV000692234, ClinVar RCV001811441, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, Aortic aneurysm, familial thoracic 6; not provided
- D58E (p.Asp58Glu), 1000Genomes rs150547139, ESP rs150547139, ExAC rs150547139, TOPMed rs150547139, REVEL 0.73, CADD 13.70, Uncertain significance, Aortic aneurysm, familial thoracic 6
- E59K (p.Glu59Lys), rs1306745024, ClinGen CA377513465, NCI-TCGA Cosmic COSV5651, ClinVar RCV000774166, REVEL 0.89, CADD 29.60, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Aortic aneurysm, famili
- A60G (p.Ala60Gly), rs2494570816, ClinGen CA377513453, ClinVar RCV003150802, REVEL 0.80, CADD 29.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A60T (p.Ala60Thr), rs794728022, ClinGen CA006851, ClinVar RCV000181016, ClinVar RCV004786494, AlphaMissense 1.00, MetaLR 0.92, Uncertain significance, not provided; Aortic aneurysm, familial thoracic 6
- S62T (p.Ser62Thr), rs2494570778, ClinGen CA377513440, ClinVar RCV004017063, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K63E (p.Lys63Glu), gnomAD rs1274364284, REVEL 0.90, CADD 29.50
- K63N (p.Lys63Asn), Ensembl rs2133270054
- R64T (p.Arg64Thr), NCI-TCGA Cosmic COSV9982, Variant assessed as somatic; moderate impact.
- I66L (p.Ile66Leu), rs1554841834, ClinGen CA377513413, ClinVar RCV000645623, Ensembl rs1554841834, AlphaMissense 0.92, MetaLR 0.82, Uncertain significance, Aortic aneurysm, familial thoracic 6
- I66T (p.Ile66Thr), Ensembl rs1589399030
- T68I (p.Thr68Ile), rs1060500132, ClinGen CA16613189, ClinVar RCV000473817, ClinVar RCV005044655, REVEL 0.88, CADD 24.90, Uncertain significance, Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction sy
- T68P (p.Thr68Pro), Ensembl rs1589399019
- L69Q (p.Leu69Gln), rs2494570603, ClinGen CA377513396, ClinVar RCV002422111, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K70N (p.Lys70Asn), rs1845969598, TOPMed rs1845969598, ClinGen CA377513387, ClinVar RCV003177007, AlphaMissense 0.97, MetaLR 0.75, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- Y71* (p.Tyr71Ter), Ensembl rs1845969494
- Y71C (p.Tyr71Cys), rs2494570548, ClinGen CA377513382, ClinVar RCV002417743, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- Y71H (p.Tyr71His), ExAC rs757701489, gnomAD rs757701489, REVEL 0.94, CADD 29.50
- P72L (p.Pro72Leu), rs1060500134, ClinGen CA16613266, ClinVar RCV000459592, ClinVar RCV000788730, REVEL 0.83, CADD 29.80, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; not provided; Aortic an
- I73T (p.Ile73Thr), rs2494570485, ClinGen CA377513368, ClinVar RCV003320030, ClinVar RCV006548516, REVEL 0.94, CADD 27.70, Conflicting interpretations, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- I73V (p.Ile73Val), NCI-TCGA Cosmic COSV9982, Variant assessed as somatic; moderate impact.
- E74* (p.Glu74Ter), NCI-TCGA Cosmic COSV5651, Variant assessed as somatic; high impact.
- H75N (p.His75Asn), rs2133269905, ClinGen CA377513358, ClinVar RCV001363094, ClinVar RCV002432022, AlphaMissense 0.98, MetaLR 0.93, Uncertain significance, Aortic aneurysm, familial thoracic 6; not provided; Familial thoracic aortic ane
- G76S (p.Gly76Ser), rs1064793016, ClinGen CA16619078, ClinVar RCV000480516, Ensembl rs1064793016, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, not provided
- I77V (p.Ile77Val), rs754716869, ClinGen CA027101, ClinVar RCV001765443, ClinVar RCV003517344, REVEL 0.74, CADD 22.70, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- I78V (p.Ile78Val), Ensembl rs1045270949
- T79I (p.Thr79Ile), Ensembl rs1564647102, Uncertain significance, Aortic aneurysm, familial thoracic 6
- N80S (p.Asn80Ser), gnomAD rs1461306311, REVEL 0.85, CADD 28.00
- D82E (p.Asp82Glu), rs1254836237, ClinGen CA377513303, ClinVar RCV000645625, ClinVar RCV002458093, AlphaMissense 0.90, MetaLR 0.73, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; Aortic aneurysm, famili
- D82N (p.Asp82Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D83N (p.Asp83Asn), rs794728023, ClinGen CA006882, NCI-TCGA Cosmic COSV9982, ClinVar RCV000181017, REVEL 0.84, CADD 23.80, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- M84T (p.Met84Thr), rs1589398956, ClinGen CA377513291, ClinVar RCV000820463, Ensembl rs1589398956, REVEL 0.95, CADD 26.70, Uncertain significance, Aortic aneurysm, familial thoracic 6
- K86E (p.Lys86Glu), rs1845968514, ClinGen CA377513277, ClinVar RCV001189025, Ensembl rs1845968514, AlphaMissense 0.99, MetaLR 0.84, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- K86N (p.Lys86Asn), NCI-TCGA TCGA novel, Uncertain significance, Aortic aneurysm, familial thoracic 6
- K86R (p.Lys86Arg), rs1554841831, ClinGen CA377513274, ClinVar RCV000645626, ClinVar RCV002458094, REVEL 0.85, CADD 32.00, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- W88R (p.Trp88Arg), rs2133261529, ClinGen CA377513010, ClinVar RCV001993861, Ensembl rs2133261529, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, Aortic aneurysm, familial thoracic 6
- S91Y (p.Ser91Tyr), TOPMed rs1265886569, gnomAD rs1265886569, REVEL 0.79, CADD 28.80
- F92L (p.Phe92Leu), rs2494555365, ClinGen CA377512979, ClinVar RCV003331615, Uncertain significance, not specified
- Y93N (p.Tyr93Asn), ExAC rs749780094
- N94D (p.Asn94Asp), rs778382397, ClinGen CA027301, ClinVar RCV002949360, ExAC rs778382397, REVEL 0.85, CADD 28.70, Uncertain significance, Aortic aneurysm, familial thoracic 6
- N94S (p.Asn94Ser), rs756569259, ClinGen CA027309, ClinVar RCV001524653, ClinVar RCV005648154, REVEL 0.77, CADD 32.00, Uncertain significance, not provided; Aortic aneurysm, familial thoracic 6; Familial thoracic aortic ane
- E95D (p.Glu95Asp), ExAC rs748465638, TOPMed rs748465638, gnomAD rs748465638, REVEL 0.85, CADD 22.80, Likely benign
- E95G (p.Glu95Gly), rs2494555199, ClinGen CA377512956, ClinVar RCV002806835, Uncertain significance, Aortic aneurysm, familial thoracic 6
- E95K (p.Glu95Lys), rs1064796442, ClinGen CA16619077, ClinVar RCV000486179, ClinVar RCV002438182, AlphaMissense 1.00, MetaLR 0.93, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; not provided
- R97C (p.Arg97Cys), rs1268825216, NCI-TCGA Cosmic COSV5651, TOPMed rs1268825216, gnomAD rs1268825216, REVEL 0.95, CADD 33.00, Variant assessed as somatic; moderate impact.
- R97H (p.Arg97His), rs1055787195, ClinGen CA211320727, ClinVar RCV003455890, ClinVar RCV004765842, REVEL 0.91, CADD 24.80, Uncertain significance, Moyamoya disease 5; not provided
- R97P (p.Arg97Pro), rs1055787195, ClinGen CA377512942, ClinVar RCV003633092, REVEL 0.95, CADD 29.90, Uncertain significance, Aortic aneurysm, familial thoracic 6
- V98I (p.Val98Ile), Ensembl rs1564645780, REVEL 0.56, CADD 22.60
- A99G (p.Ala99Gly), rs779757924, ClinGen CA027367, ClinVar RCV000439048, ClinVar RCV000585788, REVEL 0.72, CADD 29.30, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Aortic an
- E101E (p.Glu101Glu), rs757977826, gnomAD 10-88943863-T-C, CADD 9.94
- E102A (p.Glu102Ala), rs1473465595, ClinGen CA377512911, ClinVar RCV003118505, TOPMed rs1473465595, REVEL 0.94, CADD 29.50, Uncertain significance, Aortic aneurysm, familial thoracic 6
- E102Q (p.Glu102Gln), TOPMed rs1412507561, gnomAD rs1412507561, REVEL 0.88, CADD 27.40
- E102D (p.Glu102Asp), gnomAD 10-88943860-C-A, REVEL 0.63, CADD 16.90
- E102E (p.Glu102Glu), gnomAD 10-88943860-C-T, CADD 9.79
- H103H (p.His103His), rs1180253745, gnomAD 10-88943857-A-G, CADD 9.95
- H103K (p.His103Lys), gnomAD 10-88943859-G-GCT, CADD 33.00
- P104S (p.Pro104Ser), rs1156640249, ClinGen CA377512898, ClinVar RCV001805298, ClinVar RCV003633600, REVEL 0.86, CADD 26.50, Uncertain significance, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- P104P (p.Pro104Pro), rs1473725252, gnomAD 10-88943854-G-A, CADD 4.33
- P104H (p.Pro104His), gnomAD 10-88943855-G-T, REVEL 0.90, CADD 28.60
- T105I (p.Thr105Ile), TOPMed rs1343660153, gnomAD rs1343660153, REVEL 0.51, CADD 22.70, Uncertain significance, Aortic aneurysm, familial thoracic 6
- T105P (p.Thr105Pro), gnomAD 10-88943852-GT-G, CADD 32.00
- L106P (p.Leu106Pro), TOPMed rs937437219
- L106L (p.Leu106Leu), rs1845900195, gnomAD 10-88943848-C-T, CADD 9.60
- T108M (p.Thr108Met), rs886038789, ClinGen CA10587714, ClinVar RCV000251267, ClinVar RCV002058494, REVEL 0.88, CADD 28.30, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Aortic aneurysm, famili
- T108T (p.Thr108Thr), rs750005327, gnomAD 10-88943842-C-T, CADD 1.42
- T108K (p.Thr108Lys), gnomAD 10-88943843-G-T, REVEL 0.82, CADD 27.80
- E109K (p.Glu109Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E109R (p.Glu109Arg), rs2133261333, ClinGen CA2573145867, ClinVar RCV002221951, Aortic aneurysm, familial thoracic 6
- A110T (p.Ala110Thr), TOPMed rs1392926771, gnomAD rs1392926771, REVEL 0.90, CADD 27.20
- P111S (p.Pro111Ser), gnomAD 10-88943835-G-A, REVEL 0.85, CADD 27.90
- L112L (p.Leu112Leu), gnomAD 10-88943830-C-A, CADD 12.30
- N113D (p.Asn113Asp), rs2494554645, ClinGen CA377512847, ClinVar RCV003050232, Uncertain significance, Aortic aneurysm, familial thoracic 6
- N113K (p.Asn113Lys), Ensembl rs113622728, REVEL 0.82, CADD 24.10
- N113S (p.Asn113Ser), rs397516680, ClinGen CA377512845, ClinVar RCV001795827, Ensembl rs397516680, AlphaMissense 0.91, MetaLR 0.86, Uncertain significance, Aortic aneurysm, familial thoracic 6
- N113T (p.Asn113Thr), rs397516680, ClinGen CA006891, ClinVar RCV000037192, Ensembl rs397516680, AlphaMissense 0.91, MetaLR 0.86, Uncertain significance, Cardiovascular phenotype
- P114R (p.Pro114Arg), rs2133261286, ClinGen CA2573053375, ClinVar RCV001795828, Likely pathogenic
- P114S (p.Pro114Ser), NCI-TCGA Cosmic COSV5651, Variant assessed as somatic; moderate impact.
- P114P (p.Pro114Pro), gnomAD 10-88943824-G-C, CADD 11.70
- K115N (p.Lys115Asn), rs1845899710, ClinGen CA377512831, ClinVar RCV001048688, Ensembl rs1845899710, AlphaMissense 1.00, MetaLR 0.91, Uncertain significance, Aortic aneurysm, familial thoracic 6
- K115R (p.Lys115Arg), rs794728024, ClinGen CA006899, ClinVar RCV000181018, Ensembl rs794728024, AlphaMissense 0.49, MetaLR 0.88, Uncertain significance, not provided
- A116A (p.Ala116Ala), rs2133261262, gnomAD 10-88943818-G-A, CADD 13.60
- A116T (p.Ala116Thr), gnomAD 10-88943820-C-T, REVEL 0.77, CADD 23.10
- N117D (p.Asn117Asp), NCI-TCGA Cosmic COSV5651, Variant assessed as somatic; moderate impact., in AAT6
- N117S (p.Asn117Ser), rs2133261250, ClinGen CA377512819, ClinVar RCV001799142, ClinVar RCV001868905, AlphaMissense 0.78, MetaLR 0.91, Conflicting interpretations, Aortic aneurysm, familial thoracic 6; Familial thoracic aortic aneurysm and aort
- N117T (p.Asn117Thr), UniProt VAR 045915, Likely pathogenic, not provided
- R118P (p.Arg118Pro), ExAC rs112602953, gnomAD rs112602953, Pathogenic, in AAT6
- R118Q (p.Arg118Gln), rs112602953, ClinGen CA006909, NCI-TCGA Cosmic COSV5651, ClinVar RCV000181019, REVEL 0.94, CADD 29.30, Pathogenic/Likely pathogenic, Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction sy
- R118W (p.Arg118Trp), rs1845899655, ClinGen CA377512814, ClinVar RCV001362418, ClinVar RCV001806146, REVEL 0.85, CADD 27.60, Conflicting interpretations, Aortic aneurysm, familial thoracic 6; not provided; Familial thoracic aortic ane
- R118R (p.Arg118Arg), gnomAD 10-88943812-C-T, CADD 11.40
- R118L (p.Arg118Leu), gnomAD 10-88943813-C-A, REVEL 0.94, CADD 29.00
- E119K (p.Glu119Lys), Ensembl rs867537284, Uncertain significance
- E119Q (p.Glu119Gln), rs867537284, ClinGen CA377512811, ClinVar RCV002021747, Ensembl rs867537284, AlphaMissense 0.99, MetaLR 0.97, Uncertain significance, Aortic aneurysm, familial thoracic 6
- E119E (p.Glu119Glu), rs756754618, gnomAD 10-88943809-C-T, CADD 11.10
- K120N (p.Lys120Asn), ExAC rs753798493, gnomAD rs753798493, REVEL 0.88, CADD 24.40
- M121T (p.Met121Thr), rs2494554356, ClinGen CA377512795, ClinVar RCV003225601, Uncertain significance, not provided
- M121I (p.Met121Ile), gnomAD 10-88943798-TGAGT, CADD 33.00
- M121* (p.Met121Ter), gnomAD 10-88943804-AT-A, CADD 32.00
- T122T (p.Thr122Thr), rs1327833502, gnomAD 10-88943800-A-T, CADD 7.77
- T122P (p.Thr122Pro), gnomAD 10-88943802-T-G, REVEL 0.92, CADD 24.00
- Q123* (p.Gln123Ter), rs1845899288, ClinGen CA377512781, ClinVar RCV001296490, ClinVar RCV001559987, CADD 43.00, Uncertain significance
- Q123L (p.Gln123Leu), TOPMed rs1845899235
- Q123P (p.Gln123Pro), gnomAD 10-88943798-T-G, REVEL 0.93, CADD 32.00
- I124del (p.Ile124del), rs1193203168, gnomAD 10-88941864-CATA-, CADD 21.30
- M125K (p.Met125Lys), rs2133256518, ClinGen CA377512571, ClinVar RCV001799143, Ensembl rs2133256518, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- F126F (p.Phe126Phe), gnomAD 10-88941861-A-G, CADD 13.00
- E127Q (p.Glu127Gln), rs2494542984, ClinGen CA377512558, ClinVar RCV002302205, Uncertain significance, Aortic aneurysm, familial thoracic 6
- T128I (p.Thr128Ile), gnomAD rs1333659273
- T128T (p.Thr128Thr), gnomAD 10-88941855-A-C, CADD 7.98
- F129S (p.Phe129Ser), NCI-TCGA Cosmic COSV5651, Variant assessed as somatic; moderate impact.
- N130N (p.Asn130Asn), rs141933412, gnomAD 10-88941849-A-G, CADD 8.70
- V131V (p.Val131Val), rs752609914, gnomAD 10-88941846-G-A, CADD 8.60
- P132Q (p.Pro132Gln), gnomAD 10-88941843-TG-T, CADD 33.00
- P132P (p.Pro132Pro), rs1313729817, gnomAD 10-88941843-T-G, CADD 6.20
- A133S (p.Ala133Ser), Ensembl rs1845860425, REVEL 0.76, CADD 22.70
Public ACTA2 analysis runs
- ACTA2 analysis run — ACTA2 (668 variants) — completed 2026-08-18