FLG (Filaggrin) variants and mutations
FLG (also known as Filaggrin) is a human protein-coding gene encoding a filaggrin protein. It aggregates keratin fibers and is processed into natural moisturizing factors that are essential for epidermal barrier formation and hydration. Loss-of-function variants strongly predispose to ichthyosis vulgaris and atopic dermatitis by weakening the skin barrier. This analysis covers 9,805 FLG variants and mutations. Of these, 18% have computational variant effect predictions. Disease context includes atopic eczema, ichthyosis vulgaris, and Eczematoid dermatitis. Example FLG variants include S2P, T3A, and L4F.
Variant analysis overview
- Gene: FLG
- Protein: Filaggrin
- UniProt accession: P20930
- Organism: Homo sapiens
- Variants analyzed: 9805
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 9,616 unspecified-consequence records; 3 stop lost; 50 synonymous variants; 115 missense variants; 14 frameshift variants; 4 stop-gained variants; 3 in-frame deletions; 1 protein altering variant; 2 substitution
- Prediction scores: 1,716 variants have prediction scores (18% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: atopic eczema, ichthyosis vulgaris, Eczematoid dermatitis, asthma, dermatitis, skin disorder, Abnormality of the skeletal system, childhood onset asthma, dermatophytosis, contact dermatitis, allergic disease, autosomal dominant ichthyosis vulgaris.
Protein structure and variant hotspots
- Protein features: 2 domains; 5 binding sites.
- Structural context: 106 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable FLG variants
Examples include S2P, T3A, L4F, L4V, L5P, E6K, N7S, N7T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2P (p.Ser2Pro), ExAC rs746067399, TOPMed rs746067399, gnomAD rs746067399
- T3A (p.Thr3Ala), Ensembl rs79290069
- L4F (p.Leu4Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L4V (p.Leu4Val), TOPMed rs1022554255, gnomAD rs1022554255
- L5P (p.Leu5Pro), ExAC rs779302206, TOPMed rs779302206, gnomAD rs779302206
- E6K (p.Glu6Lys), rs865914246, NCI-TCGA Cosmic COSV6424, Ensembl rs865914246, AlphaMissense 0.56, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- N7S (p.Asn7Ser), ESP rs372700376, TOPMed rs372700376, gnomAD rs372700376, Uncertain significance
- N7T (p.Asn7Thr), rs372700376, ClinGen CA342110565, ClinVar RCV004386758, ESP rs372700376, AlphaMissense 0.58, MetaLR 0.00, Uncertain significance, Inborn genetic diseases
- I8F (p.Ile8Phe), Ensembl rs1652753562
- I8T (p.Ile8Thr), TOPMed rs1652753270
- F9L (p.Phe9Leu), TOPMed rs1652752999, gnomAD rs1652752999
- F9V (p.Phe9Val), NCI-TCGA Cosmic COSV6423, Variant assessed as somatic; moderate impact.
- A10V (p.Ala10Val), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- I11V (p.Ile11Val), gnomAD rs1259944011
- I12V (p.Ile12Val), Ensembl rs1652752777
- N13K (p.Asn13Lys), ESP rs147265288, ExAC rs147265288, TOPMed rs147265288, gnomAD rs147265288
- F15L (p.Phe15Leu), ExAC rs753265372, gnomAD rs753265372
- F15S (p.Phe15Ser), rs1487842274, NCI-TCGA Cosmic COSV1009, gnomAD rs1487842274, AlphaMissense 0.99, MetaLR 0.34, Variant assessed as somatic; moderate impact.
- K16M (p.Lys16Met), ExAC rs767834113, gnomAD rs767834113
- K16N (p.Lys16Asn), Ensembl rs2485518
- Q17E (p.Gln17Glu), 1000Genomes rs2485517
- Q17K (p.Gln17Lys), 1000Genomes rs2485517
- Y18* (p.Tyr18Ter), NCI-TCGA Cosmic COSV6425, Variant assessed as somatic; high impact.
- Y18H (p.Tyr18His), TOPMed rs1283132171, gnomAD rs1283132171
- S19* (p.Ser19Ter), Ensembl rs79059833
- S19P (p.Ser19Pro), TOPMed rs1557883349
- K20E (p.Lys20Glu), rs751162672, ExAC rs751162672, gnomAD rs751162672, AlphaMissense 0.33, MetaLR 0.01, Uncertain significance, Inborn genetic diseases
- K21E (p.Lys21Glu), rs2525228329, ClinGen CA342110295, ClinVar RCV002855773, Uncertain significance, Inborn genetic diseases
- K21R (p.Lys21Arg), Ensembl rs999085020
- D22E (p.Asp22Glu), ExAC rs765977346, gnomAD rs765977346
- D22H (p.Asp22His), TOPMed rs1235520980
- D22I (p.Asp22Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K23* (p.Lys23Ter), ExAC rs762458302, gnomAD rs762458302
- N24I (p.Asn24Ile), TOPMed rs903052511, gnomAD rs903052511
- N24S (p.Asn24Ser), TOPMed rs903052511, gnomAD rs903052511, Uncertain significance, Inborn genetic diseases
- D26N (p.Asp26Asn), rs73007748, ClinGen CA1108111, ClinVar RCV000886323, 1000Genomes rs73007748, AlphaMissense 0.20, MetaLR 0.03, Benign, not provided
- T27I (p.Thr27Ile), gnomAD rs1168948116
- L28S (p.Leu28Ser), Ensembl rs2101654349
- K30* (p.Lys30Ter), TOPMed rs1652749009
- K31I (p.Lys31Ile), gnomAD rs1652748910
- E32* (p.Glu32Ter), rs114733570, ClinGen CA1108108, ClinVar RCV000300225, ClinVar RCV000709724, Pathogenic
- E32D (p.Glu32Asp), TOPMed rs1652748480, gnomAD rs1652748480
- L33P (p.Leu33Pro), gnomAD rs1224396485
- E35K (p.Glu35Lys), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- L36F (p.Leu36Phe), TOPMed rs1250746880, gnomAD rs1250746880
- L36P (p.Leu36Pro), ExAC rs768524951, gnomAD rs768524951
- E38K (p.Glu38Lys), NCI-TCGA Cosmic COSV6423, Variant assessed as somatic; moderate impact.
- E38Q (p.Glu38Gln), NCI-TCGA Cosmic COSV6423, Variant assessed as somatic; moderate impact.
- K39N (p.Lys39Asn), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- E40D (p.Glu40Asp), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- E40K (p.Glu40Lys), Ensembl rs2101654324
- E40Q (p.Glu40Gln), NCI-TCGA Cosmic COSV6423, NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- F41C (p.Phe41Cys), ExAC rs746834740, gnomAD rs746834740
- F41I (p.Phe41Ile), gnomAD rs1652747752
- R42Q (p.Arg42Gln), ExAC rs771075649, TOPMed rs771075649, gnomAD rs771075649, Uncertain significance, not provided
- R42W (p.Arg42Trp), rs138819199, NCI-TCGA Cosmic COSV6423, ESP rs138819199, ExAC rs138819199, AlphaMissense 0.26, MetaLR 0.03, Uncertain significance, Inborn genetic diseases
- I44T (p.Ile44Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L45P (p.Leu45Pro), TOPMed rs1652746739
- L45R (p.Leu45Arg), TOPMed rs1652746739
- N47D (p.Asn47Asp), ExAC rs758847783, TOPMed rs758847783, gnomAD rs758847783, Uncertain significance, Inborn genetic diseases
- N47K (p.Asn47Lys), rs2525223334, ClinGen CA342109589, ClinVar RCV004386748, Uncertain significance, Inborn genetic diseases
- P48S (p.Pro48Ser), gnomAD rs1461382595
- D50E (p.Asp50Glu), Ensembl rs901764347
- D50G (p.Asp50Gly), rs115489580, ClinGen CA1108073, ClinVar RCV001618000, ClinVar RCV003956299, AlphaMissense 0.93, MetaLR 0.10, Benign, not provided
- P51A (p.Pro51Ala), 1000Genomes rs148520067, ExAC rs148520067, TOPMed rs148520067, gnomAD rs148520067
- P51S (p.Pro51Ser), 1000Genomes rs148520067, ExAC rs148520067, TOPMed rs148520067, gnomAD rs148520067
- D52E (p.Asp52Glu), TOPMed rs1652713477, gnomAD rs1652713477
- D52H (p.Asp52His), TOPMed rs1473403057, gnomAD rs1473403057
- D52N (p.Asp52Asn), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- D52V (p.Asp52Val), rs753416194, ClinGen CA1108071, ClinVar RCV002738613, ExAC rs753416194, AlphaMissense 0.76, MetaLR 0.08, Uncertain significance, Inborn genetic diseases
- M53I (p.Met53Ile), TOPMed rs1652713307
- M53T (p.Met53Thr), gnomAD rs1156337712
- V54A (p.Val54Ala), TOPMed rs1351899004, gnomAD rs1351899004
- V54L (p.Val54Leu), rs1225860917, ClinGen CA342109432, ClinVar RCV003304701, TOPMed rs1225860917, AlphaMissense 0.87, MetaLR 0.01, Uncertain significance
- D55E (p.Asp55Glu), ExAC rs763759026, TOPMed rs763759026, gnomAD rs763759026
- D55G (p.Asp55Gly), TOPMed rs1652713063
- F57L (p.Phe57Leu), ExAC rs760681209, TOPMed rs760681209, gnomAD rs760681209
- D59G (p.Asp59Gly), gnomAD rs1385160385, REVEL 0.22, CADD 24.30
- H60R (p.His60Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H60Y (p.His60Tyr), 1000Genomes rs201998175, ESP rs201998175, ExAC rs201998175, TOPMed rs201998175
- L61F (p.Leu61Phe), gnomAD rs1652712690
- D62N (p.Asp62Asn), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- D62V (p.Asp62Val), ExAC rs767191408, gnomAD rs767191408
- I63R (p.Ile63Arg), ExAC rs759395508, TOPMed rs759395508, gnomAD rs759395508
- I63T (p.Ile63Thr), ExAC rs759395508, TOPMed rs759395508, gnomAD rs759395508
- I63V (p.Ile63Val), gnomAD rs1346048704
- D64H (p.Asp64His), rs773267945, NCI-TCGA Cosmic COSV6423, ExAC rs773267945, TOPMed rs773267945, AlphaMissense 0.95, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- D64N (p.Asp64Asn), ExAC rs773267945, TOPMed rs773267945, gnomAD rs773267945
- D64V (p.Asp64Val), Ensembl rs1652712201
- H65N (p.His65Asn), ExAC rs770009613, TOPMed rs770009613, gnomAD rs770009613
- H65R (p.His65Arg), ESP rs145346832, ExAC rs145346832, TOPMed rs145346832, gnomAD rs145346832
- N66S (p.Asn66Ser), gnomAD rs1179576177
- K67N (p.Lys67Asn), ExAC rs749328294, TOPMed rs749328294, gnomAD rs749328294
- K68N (p.Lys68Asn), ExAC rs747451295, TOPMed rs747451295, gnomAD rs747451295
- I69L (p.Ile69Leu), ExAC rs780631848, gnomAD rs780631848
- I69T (p.Ile69Thr), ExAC rs758648098, TOPMed rs758648098, gnomAD rs758648098
- D70A (p.Asp70Ala), gnomAD rs1362188544
- D70H (p.Asp70His), TOPMed rs931474879, gnomAD rs931474879
- D70N (p.Asp70Asn), TOPMed rs931474879, gnomAD rs931474879
- D70V (p.Asp70Val), gnomAD rs1362188544
- D70Y (p.Asp70Tyr), TOPMed rs931474879, gnomAD rs931474879
- T72N (p.Thr72Asn), ExAC rs746246378, gnomAD rs746246378
- E73A (p.Glu73Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E73Q (p.Glu73Gln), NCI-TCGA Cosmic COSV1009, TOPMed rs1652710702, Variant assessed as somatic; moderate impact.
- L75F (p.Leu75Phe), ExAC rs778369045, TOPMed rs778369045, gnomAD rs778369045
- L75P (p.Leu75Pro), Ensembl rs1652710390
- L76V (p.Leu76Val), ESP rs370154185, ExAC rs370154185, TOPMed rs370154185, gnomAD rs370154185
- M77I (p.Met77Ile), rs1358450049, gnomAD rs1358450049, AlphaMissense 0.98, MetaLR 0.03, Variant assessed as somatic; moderate impact.
- M77T (p.Met77Thr), gnomAD rs1398381546
- V78A (p.Val78Ala), gnomAD rs1652709887
- V78I (p.Val78Ile), ExAC rs753608358, TOPMed rs753608358, gnomAD rs753608358, Likely benign, Inborn genetic diseases
- V78L (p.Val78Leu), ExAC rs753608358, TOPMed rs753608358, gnomAD rs753608358
- K80N (p.Lys80Asn), ExAC rs763670992, TOPMed rs763670992, gnomAD rs763670992, Uncertain significance, Inborn genetic diseases
- A82S (p.Ala82Ser), Ensembl rs2101653710
- Q83* (p.Gln83Ter), NCI-TCGA Cosmic COSV6423, Variant assessed as somatic; high impact.
- Q83E (p.Gln83Glu), gnomAD rs1162536390
- Q83R (p.Gln83Arg), TOPMed rs1187386591
- Y85C (p.Tyr85Cys), ExAC rs755737937, TOPMed rs755737937, gnomAD rs755737937, Uncertain significance, Inborn genetic diseases
- Y85H (p.Tyr85His), gnomAD rs1404251529
- Y86* (p.Tyr86Ter), ExAC rs759189084, gnomAD rs759189084
- Y86C (p.Tyr86Cys), ExAC rs767524129, TOPMed rs767524129, gnomAD rs767524129
- Y86H (p.Tyr86His), ESP rs367585948, ExAC rs367585948, TOPMed rs367585948, gnomAD rs367585948
- E87K (p.Glu87Lys), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- E87V (p.Glu87Val), TOPMed rs1652708771
- S88Y (p.Ser88Tyr), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- T89I (p.Thr89Ile), Ensembl rs1252268984
- K91E (p.Lys91Glu), gnomAD rs1489645220
- K91R (p.Lys91Arg), ExAC rs751384298, gnomAD rs751384298
- E92D (p.Glu92Asp), TOPMed rs1652708246, gnomAD rs1652708246
- E92K (p.Glu92Lys), gnomAD rs1221391004
- E92R (p.Glu92Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- N93I (p.Asn93Ile), rs199918968, ClinGen CA1108046, ClinVar RCV002703261, ClinVar RCV005929224, AlphaMissense 0.29, MetaLR 0.00, Uncertain significance, Inborn genetic diseases
- L94S (p.Leu94Ser), TOPMed rs1652708076
- P95A (p.Pro95Ala), ExAC rs762018918, gnomAD rs762018918
- P95L (p.Pro95Leu), rs76438926, ClinGen CA1108044, ClinVar RCV001609041, ClinVar RCV003956294, AlphaMissense 0.15, MetaLR 0.00, Benign, not provided
- P95Q (p.Pro95Gln), 1000Genomes rs76438926, ESP rs76438926, ExAC rs76438926, TOPMed rs76438926, Benign
- P95R (p.Pro95Arg), 1000Genomes rs76438926, ESP rs76438926, ExAC rs76438926, TOPMed rs76438926, Benign
- P95T (p.Pro95Thr), ExAC rs762018918, gnomAD rs762018918
- I96M (p.Ile96Met), TOPMed rs1652707522
- I96T (p.Ile96Thr), Ensembl rs80252243
- S97T (p.Ser97Thr), gnomAD rs1284115966
- G98E (p.Gly98Glu), rs1405351834, NCI-TCGA Cosmic COSV6424, gnomAD rs1405351834, AlphaMissense 0.35, MetaLR 0.00, Variant assessed as somatic; moderate impact.
- G98R (p.Gly98Arg), Ensembl rs1557882873
- H99N (p.His99Asn), ESP rs374663403, ExAC rs374663403, TOPMed rs374663403, gnomAD rs374663403
- H99R (p.His99Arg), NCI-TCGA Cosmic COSV6425, Variant assessed as somatic; moderate impact.
- K100N (p.Lys100Asn), gnomAD rs1457338677
- K100R (p.Lys100Arg), ExAC rs775791704, gnomAD rs775791704
- R102I (p.Arg102Ile), rs770230856, ClinGen CA1108039, ClinVar RCV004386780, ExAC rs770230856, AlphaMissense 0.42, MetaLR 0.00, Uncertain significance, Inborn genetic diseases
- K103E (p.Lys103Glu), Ensembl rs2101653616
- K103N (p.Lys103Asn), rs201066653, ESP rs201066653, ExAC rs201066653, TOPMed rs201066653, AlphaMissense 0.55, MetaLR 0.00, Variant assessed as somatic; moderate impact.
- K103R (p.Lys103Arg), NCI-TCGA Cosmic COSV6423, Variant assessed as somatic; moderate impact.
- H104N (p.His104Asn), ExAC rs748929953, gnomAD rs748929953
- H104Q (p.His104Gln), rs777594283, ClinGen CA1108035, ClinVar RCV004386783, ExAC rs777594283, AlphaMissense 0.37, MetaLR 0.00, Uncertain significance, Inborn genetic diseases
- H104Y (p.His104Tyr), NCI-TCGA Cosmic COSV6424, ExAC rs748929953, gnomAD rs748929953, Variant assessed as somatic; moderate impact.
- S105I (p.Ser105Ile), NCI-TCGA Cosmic COSV6424, REVEL 0.32, CADD 22.30, Variant assessed as somatic; moderate impact.
- S105R (p.Ser105Arg), TOPMed rs1652706456, REVEL 0.29, CADD 19.30
- H107L (p.His107Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H107Q (p.His107Gln), Ensembl rs975925157
- D108N (p.Asp108Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K109E (p.Lys109Glu), NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- H110Q (p.His110Gln), gnomAD rs1481232523
- H110Y (p.His110Tyr), 1000Genomes rs185700449, ExAC rs185700449, TOPMed rs185700449, gnomAD rs185700449
- E111* (p.Glu111Ter), NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; high impact.
- E111K (p.Glu111Lys), rs1240146425, NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6424, TOPMed rs1240146425, AlphaMissense 0.15, MetaLR 0.00, Variant assessed as somatic; moderate impact.
- D112N (p.Asp112Asn), ExAC rs752258821, gnomAD rs752258821
- Q115H (p.Gln115His), rs754930940, ExAC rs754930940, TOPMed rs754930940, gnomAD rs754930940, AlphaMissense 0.33, MetaLR 0.00, Uncertain significance, Inborn genetic diseases
- Q115L (p.Gln115Leu), ESP rs370754859, TOPMed rs370754859, gnomAD rs370754859, Uncertain significance
- Q115R (p.Gln115Arg), ESP rs370754859, TOPMed rs370754859, gnomAD rs370754859, Uncertain significance, Inborn genetic diseases
- E116K (p.Glu116Lys), rs751519390, NCI-TCGA Cosmic COSV6423, ExAC rs751519390, TOPMed rs751519390, AlphaMissense 0.20, MetaLR 0.00, Variant assessed as somatic; moderate impact.
- E117Q (p.Glu117Gln), ExAC rs766140277, gnomAD rs766140277
- N118Y (p.Asn118Tyr), TOPMed rs1652703857
- K119I (p.Lys119Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E120K (p.Glu120Lys), NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6424, Variant assessed as somatic; moderate impact.
- N121I (p.Asn121Ile), gnomAD rs1386182975
- R122I (p.Arg122Ile), gnomAD rs1652703326
- R122K (p.Arg122Lys), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- R124I (p.Arg124Ile), ExAC rs754018350, TOPMed rs754018350, gnomAD rs754018350
- R124S (p.Arg124Ser), TOPMed rs1652701588, gnomAD rs1652701588
- R124T (p.Arg124Thr), ExAC rs754018350, TOPMed rs754018350, gnomAD rs754018350
- P125A (p.Pro125Ala), TOPMed rs1652700844
Public FLG analysis runs
- FLG analysis run — FLG (9,805 variants) — completed 2026-08-21