ACAN (Aggrecan core protein) variants and mutations
ACAN (also known as Aggrecan core protein) is a human protein-coding gene encoding an aggrecan core protein. Its highly charged glycosaminoglycan-rich structure enables cartilage to retain water and resist compressive forces, making it essential for growth-plate and articular-cartilage mechanics. Pathogenic variants can cause short-stature and skeletal-dysplasia phenotypes, including spondyloepimetaphyseal dysplasia and familial osteochondritis dissecans. This analysis covers 3,035 ACAN variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes spondyloepimetaphyseal dysplasia, aggrecan type, Familial osteochondritis dissecans, and spondyloepiphyseal dysplasia, Kimberley type. Example ACAN variants include M1I, T2I, and T2T.
Variant analysis overview
- Gene: ACAN
- Protein: Aggrecan core protein
- UniProt accession: P16112
- Organism: Homo sapiens
- Variants analyzed: 3035
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 2,722 unspecified-consequence records; 127 synonymous variants; 165 missense variants; 8 frameshift variants; 3 in-frame deletions; 7 stop-gained variants; 2 splice-region variants; 1 substitution
- Prediction scores: 2,325 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: spondyloepimetaphyseal dysplasia, aggrecan type, Familial osteochondritis dissecans, spondyloepiphyseal dysplasia, Kimberley type, osteochondritis dissecans, Abnormality of the skeletal system, hereditary disease, osteoarthritis, knee, osteoarthritis, hip, spondyloepiphyseal dysplasia, osteoarthritis, Dupuytren Contracture, hearing loss disorder.
Protein structure and variant hotspots
- Protein features: 8 domains; 10 binding sites; 18 post-translational modification sites.
- Structural context: 1,189 variants have structural context.
- PTM context: 23 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ACAN variants
Examples include M1I, T2I, T2T, T3I, T3N, T3A, T3T, L4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1057522582, ClinGen CA16607047, ClinVar RCV000419116, MetaLR 0.03, MetaSVM -1.12, Uncertain significance, not provided
- T2I (p.Thr2Ile), ExAC rs770071622, TOPMed rs770071622, gnomAD rs770071622, CADD 24.70, PolyPhen-2 0.91, Uncertain significance, not provided
- T2T (p.Thr2Thr), rs775539020, gnomAD 15-88836212-C-T, CADD 11.00
- T3I (p.Thr3Ile), TOPMed rs1896499281, gnomAD rs1896499281
- T3N (p.Thr3Asn), TOPMed rs1896499281, gnomAD rs1896499281, CADD 25.20, PolyPhen-2 0.97
- T3A (p.Thr3Ala), gnomAD 15-88836213-A-G, CADD 24.80, PolyPhen-2 0.89
- T3T (p.Thr3Thr), rs1474930785, gnomAD 15-88836215-T-A, CADD 11.40
- L4S (p.Leu4Ser), rs202166561, ClinGen CA7719112, ClinVar RCV001972215, ESP rs202166561, CADD 25.00, PolyPhen-2 0.70, Conflicting interpretations, not provided
- L4L (p.Leu4Leu), rs1896499388, gnomAD 15-88836216-T-C, CADD 10.50
- L5F (p.Leu5Phe), rs371249232, ClinGen CA7719113, ClinVar RCV003115980, ESP rs371249232, CADD 22.90, PolyPhen-2 0.18, Uncertain significance, not provided
- L5P (p.Leu5Pro), Ensembl rs1363665841
- W6* (p.Trp6Ter), rs1447022229, ClinGen CA393713678, ClinVar RCV003325794, TOPMed rs1447022229, AlphaMissense 0.32, MetaLR 0.00, Pathogenic
- W6R (p.Trp6Arg), TOPMed rs1300824260
- W6S (p.Trp6Ser), TOPMed rs1447022229, Uncertain significance
- W6C (p.Trp6Cys), gnomAD 15-88836222-TGG-T, CADD 23.60
- V7D (p.Val7Asp), gnomAD 15-88836225-G-GAC, CADD 25.30
- F8Y (p.Phe8Tyr), gnomAD 15-88836227-T-TTA, CADD 24.40
- F8S (p.Phe8Ser), gnomAD 15-88836229-T-C, CADD 24.00, PolyPhen-2 0.31
- F8F (p.Phe8Phe), rs1359613917, gnomAD 15-88836230-C-T, CADD 9.59
- V9L (p.Val9Leu), rs776631256, ClinGen CA393713715, ClinVar RCV004552401, AlphaMissense 0.38, MetaLR 0.01, Uncertain significance, ACAN-related disorder
- V9M (p.Val9Met), rs776631256, ClinGen CA7719114, cosmic curated COSV10441, ClinVar RCV002734778, AlphaMissense 0.38, MetaLR 0.01, Uncertain significance, not provided; Inborn genetic diseases
- V9V (p.Val9Val), rs760468016, gnomAD 15-88836233-G-C, CADD 8.23
- T10S (p.Thr10Ser), TOPMed rs1422976124, gnomAD rs1422976124, CADD 19.10, PolyPhen-2 0.02
- T10I (p.Thr10Ile), gnomAD 15-88836235-C-T, CADD 22.80, PolyPhen-2 0.36
- L11V (p.Leu11Val), gnomAD rs1383270733
- L11M (p.Leu11Met), gnomAD 15-88836237-C-A, CADD 24.90, PolyPhen-2 1.00
- L11L (p.Leu11Leu), rs1383270733, gnomAD 15-88836237-C-T, CADD 11.10
- V13V (p.Val13Val), rs1298310048, gnomAD 15-88836245-C-A, CADD 11.80
- A16V (p.Ala16Val), gnomAD rs1325083323, CADD 26.00, PolyPhen-2 0.94, Uncertain significance, not provided
- A16A (p.Ala16Ala), rs1227210877, gnomAD 15-88836254-A-C, CADD 5.16
- A17S (p.Ala17Ser), ExAC rs766063753, TOPMed rs766063753, gnomAD rs766063753, CADD 15.80, PolyPhen-2 0.45
- A17V (p.Ala17Val), rs761719517, ClinGen CA274501339, ClinVar RCV001758905, TOPMed rs761719517, CADD 13.20, PolyPhen-2 0.10, Uncertain significance, not provided
- V18F (p.Val18Phe), TOPMed rs1896500943
- V18V (p.Val18Val), rs753706123, gnomAD 15-88836260-C-A, CADD 4.50
- T19S (p.Thr19Ser), gnomAD 15-88836262-C-G, CADD 8.06, PolyPhen-2 0.00
- E21Q (p.Glu21Gln), ExAC rs754672128, gnomAD rs754672128, CADD 23.50, PolyPhen-2 0.71
- E21K (p.Glu21Lys), gnomAD 15-88836267-G-A, CADD 23.10, PolyPhen-2 0.52
- T22I (p.Thr22Ile), gnomAD 15-88836271-C-T, CADD 13.40, PolyPhen-2 0.01
- T22T (p.Thr22Thr), gnomAD 15-88836272-T-A, CADD 6.36
- D24E (p.Asp24Glu), rs571206900, ClinGen CA7719136, ClinVar RCV002077456, ClinVar RCV002550519, CADD 14.60, PolyPhen-2 0.03, Conflicting interpretations, Inborn genetic diseases; not provided
- H25N (p.His25Asn), gnomAD rs1198280822, CADD 15.40, PolyPhen-2 0.08
- H25R (p.His25Arg), gnomAD 15-88838666-A-G, CADD 13.90, PolyPhen-2 0.01
- H25H (p.His25His), gnomAD 15-88838667-T-C, CADD 8.76
- D26E (p.Asp26Glu), TOPMed rs1250848987, gnomAD rs1250848987, CADD 19.70, PolyPhen-2 0.60
- D26G (p.Asp26Gly), Ensembl rs1896566574, CADD 22.60, PolyPhen-2 0.04
- D26N (p.Asp26Asn), gnomAD 15-88838668-G-A, CADD 24.30, PolyPhen-2 0.68
- N27D (p.Asn27Asp), rs1329297647, ClinGen CA393714690, ClinVar RCV001893785, TOPMed rs1329297647, CADD 20.50, PolyPhen-2 0.01, Uncertain significance, not provided
- N27S (p.Asn27Ser), rs752419278, ClinGen CA7719137, ClinVar RCV002657880, ClinVar RCV006292229, CADD 17.30, PolyPhen-2 0.02, Uncertain significance, not provided; Inborn genetic diseases
- N27N (p.Asn27Asn), rs1156388964, gnomAD 15-88838673-C-T, CADD 8.34
- S28L (p.Ser28Leu), 1000Genomes rs148320028, ExAC rs148320028, TOPMed rs148320028, gnomAD rs148320028, CADD 20.40, PolyPhen-2 0.00
- S28W (p.Ser28Trp), 1000Genomes rs148320028, ExAC rs148320028, TOPMed rs148320028, gnomAD rs148320028, CADD 24.20, PolyPhen-2 0.83
- S28S (p.Ser28Ser), gnomAD 15-88838676-G-T, CADD 0.44
- L29P (p.Leu29Pro), Ensembl rs1896567307
- L29L (p.Leu29Leu), rs1438439224, gnomAD 15-88838677-C-T, CADD 8.24
- L29V (p.Leu29Val), gnomAD 15-88838677-C-G, CADD 23.50, PolyPhen-2 0.99
- S30N (p.Ser30Asn), rs1324649266, ClinGen CA393714709, ClinVar RCV002299602, TOPMed rs1324649266, CADD 25.70, Uncertain significance, not provided
- S30R (p.Ser30Arg), ExAC rs751144925, gnomAD rs751144925, CADD 22.70, PolyPhen-2 0.37
- S30T (p.Ser30Thr), gnomAD 15-88838681-G-C, CADD 25.50, PolyPhen-2 0.79
- S30S (p.Ser30Ser), gnomAD 15-88838682-T-C, CADD 7.51
- V31F (p.Val31Phe), rs1041254006, ClinGen CA393714714, cosmic curated COSV10967, ClinVar RCV002226435, AlphaMissense 0.72, MetaLR 0.06, Uncertain significance, Short stature and advanced bone age, with or without early-onset osteoarthritis
- V31I (p.Val31Ile), TOPMed rs1041254006, AlphaMissense 0.72, MetaLR 0.06, Uncertain significance
- V31V (p.Val31Val), gnomAD 15-88838685-C-A, CADD 7.92
- S32R (p.Ser32Arg), gnomAD 15-88838686-A-C, CADD 24.50, PolyPhen-2 0.77
- S32T (p.Ser32Thr), gnomAD 15-88838687-G-C, CADD 25.30, PolyPhen-2 0.79
- I33M (p.Ile33Met), ExAC rs757687541, gnomAD rs757687541
- I33I (p.Ile33Ile), gnomAD 15-88838691-C-T, CADD 10.20
- P34S (p.Pro34Ser), cosmic curated COSV61359, 1000Genomes rs550784997, ExAC rs550784997, TOPMed rs550784997, CADD 24.90, PolyPhen-2 0.99, Uncertain significance, not specified
- P34T (p.Pro34Thr), 1000Genomes rs550784997, ExAC rs550784997, TOPMed rs550784997, gnomAD rs550784997, CADD 24.50, PolyPhen-2 0.91
- P34R (p.Pro34Arg), gnomAD 15-88838693-C-G, CADD 25.30, PolyPhen-2 1.00
- P34P (p.Pro34Pro), gnomAD 15-88838694-C-A, CADD 2.76
- Q35L (p.Gln35Leu), ExAC rs746169178
- Q35P (p.Gln35Pro), ExAC rs746169178
- Q35Q (p.Gln35Gln), gnomAD 15-88838697-A-G, CADD 0.25
- P36L (p.Pro36Leu), cosmic curated COSV61356, TOPMed rs1374390440, gnomAD rs1374390440, CADD 23.50, PolyPhen-2 0.85
- P36S (p.Pro36Ser), rs770179538, ClinGen CA7719144, ClinVar RCV003664866, ExAC rs770179538, CADD 23.50, PolyPhen-2 0.74, Uncertain significance, not provided
- P36P (p.Pro36Pro), rs569119258, gnomAD 15-88838700-G-T, CADD 0.09
- S37F (p.Ser37Phe), Ensembl rs919876046, CADD 23.90, PolyPhen-2 0.94
- S37P (p.Ser37Pro), 1000Genomes rs536525136, ExAC rs536525136, gnomAD rs536525136, CADD 24.50, PolyPhen-2 0.91
- S37S (p.Ser37Ser), gnomAD 15-88838703-C-A, CADD 6.63
- P38L (p.Pro38Leu), rs548534627, ClinGen CA7719147, ClinVar RCV002129751, ClinVar RCV003025429, CADD 24.40, PolyPhen-2 1.00, Conflicting interpretations, not provided; Inborn genetic diseases; not specified
- P38R (p.Pro38Arg), gnomAD 15-88838705-C-G, CADD 24.10, PolyPhen-2 1.00
- P38P (p.Pro38Pro), rs367956651, gnomAD 15-88838706-G-T, CADD 0.08
- L39Q (p.Leu39Gln), Ensembl rs2141563150
- L39V (p.Leu39Val), gnomAD 15-88838707-C-G, CADD 7.36, PolyPhen-2 0.10
- R40K (p.Arg40Lys), ExAC rs748319031, TOPMed rs748319031, gnomAD rs748319031, CADD 14.40, PolyPhen-2 0.01, Uncertain significance, not provided
- R40S (p.Arg40Ser), TOPMed rs374081272, gnomAD rs374081272, CADD 19.80, PolyPhen-2 0.24
- R40R (p.Arg40Arg), rs374081272, gnomAD 15-88838712-G-A, CADD 6.27
- V41I (p.Val41Ile), gnomAD 15-88838713-G-A, CADD 24.10, PolyPhen-2 0.46
- L42V (p.Leu42Val), gnomAD rs1896568910, CADD 15.10, PolyPhen-2 0.07, Uncertain significance, not provided
- L42F (p.Leu42Phe), gnomAD 15-88838716-C-T, CADD 23.90, PolyPhen-2 0.80
- L42L (p.Leu42Leu), rs1189816083, gnomAD 15-88838718-C-G, CADD 5.92
- L43V (p.Leu43Val), TOPMed rs1269536364, gnomAD rs1269536364, CADD 24.20
- L43L (p.Leu43Leu), rs770715922, gnomAD 15-88838721-G-C, CADD 4.35
- G44A (p.Gly44Ala), gnomAD rs1896569344, CADD 25.80, PolyPhen-2 0.99
- G44R (p.Gly44Arg), rs1896569256, ClinGen CA393714784, NCI-TCGA Cosmic COSV6136, cosmic curated COSV61360, CADD 27.50, PolyPhen-2 1.00, Uncertain significance, Osteochondritis dissecans
- G44G (p.Gly44Gly), rs1221534302, gnomAD 15-88838724-G-A, CADD 7.21
- T45N (p.Thr45Asn), rs759354442, ClinGen CA7719152, ClinVar RCV003063090, ExAC rs759354442, CADD 14.00, PolyPhen-2 0.01, Uncertain significance, not provided
- T45P (p.Thr45Pro), Ensembl rs1596130612, CADD 22.70, PolyPhen-2 0.20
- T45A (p.Thr45Ala), gnomAD 15-88838725-A-G, CADD 22.00, PolyPhen-2 0.01
- T45S (p.Thr45Ser), gnomAD 15-88838726-C-G, CADD 8.85, PolyPhen-2 0.00
- T45T (p.Thr45Thr), rs372517447, gnomAD 15-88838727-C-T, CADD 6.74
- L47F (p.Leu47Phe), ExAC rs775463088, TOPMed rs775463088, gnomAD rs775463088, CADD 23.20, PolyPhen-2 0.85
- L47L (p.Leu47Leu), rs368322348, gnomAD 15-88838733-C-T, CADD 8.56
- T48I (p.Thr48Ile), rs1279018978, ClinGen CA393714811, ClinVar RCV003712116, TOPMed rs1279018978, CADD 24.10, PolyPhen-2 0.67, Uncertain significance, not provided
- T48P (p.Thr48Pro), Ensembl rs1596130645
- I49M (p.Ile49Met), rs1249230063, ClinGen CA393714818, ClinVar RCV003550321, gnomAD rs1249230063, CADD 24.70, PolyPhen-2 0.99, Uncertain significance, not provided
- I49I (p.Ile49Ile), gnomAD 15-88838739-C-T, CADD 11.40
- P50S (p.Pro50Ser), rs2505221247, ClinGen CA393714821, ClinVar RCV003710929, Uncertain significance, not provided
- Y52H (p.Tyr52His), gnomAD 15-88838746-T-C, CADD 26.90, PolyPhen-2 0.99
- Y52C (p.Tyr52Cys), gnomAD 15-88838747-A-G, CADD 28.70, PolyPhen-2 0.99
- F53L (p.Phe53Leu), gnomAD 15-88838751-C-A, CADD 23.60, PolyPhen-2 0.30
- I54V (p.Ile54Val), TOPMed rs1220719528, gnomAD rs1220719528, CADD 20.10, PolyPhen-2 0.08
- I54I (p.Ile54Ile), rs377037099, gnomAD 15-88838754-C-T, CADD 10.20
- D55G (p.Asp55Gly), rs370110892, ClinGen CA7719158, ClinVar RCV002579366, ClinVar RCV005782373, CADD 24.40, PolyPhen-2 0.69, Uncertain significance, Inborn genetic diseases; not provided
- D55H (p.Asp55His), rs763861381, ClinGen CA393714856, ClinVar RCV002628199, CADD 22.10, PolyPhen-2 0.16, Uncertain significance, not provided
- D55N (p.Asp55Asn), ExAC rs763861381, TOPMed rs763861381, gnomAD rs763861381, CADD 22.00, PolyPhen-2 0.17
- D55Y (p.Asp55Tyr), ExAC rs763861381, TOPMed rs763861381, gnomAD rs763861381, CADD 25.10, PolyPhen-2 0.88
- D55D (p.Asp55Asp), rs1043116010, gnomAD 15-88838757-C-T, CADD 9.57
- P56S (p.Pro56Ser), gnomAD 15-88838758-C-T, CADD 20.90, PolyPhen-2 0.14
- P56L (p.Pro56Leu), gnomAD 15-88838759-C-T, CADD 23.40, PolyPhen-2 0.22
- P56P (p.Pro56Pro), rs534678891, gnomAD 15-88838760-C-T, CADD 9.76
- M57I (p.Met57Ile), ExAC rs750953875, TOPMed rs750953875, gnomAD rs750953875, CADD 17.20, PolyPhen-2 0.00
- M57T (p.Met57Thr), TOPMed rs998783686, CADD 12.50, PolyPhen-2 0.00
- M57V (p.Met57Val), TOPMed rs1159549993, gnomAD rs1159549993, CADD 4.69, PolyPhen-2 0.00, Uncertain significance, not provided
- M57K (p.Met57Lys), gnomAD 15-88838762-T-A, CADD 15.40, PolyPhen-2 0.05
- H58N (p.His58Asn), TOPMed rs1896571026, gnomAD rs1896571026, CADD 24.40, PolyPhen-2 0.79
- H58P (p.His58Pro), gnomAD rs1463725285, CADD 24.80, PolyPhen-2 0.86
- H58Y (p.His58Tyr), gnomAD 15-88838764-C-T, CADD 24.60, PolyPhen-2 0.86
- H58R (p.His58Arg), gnomAD 15-88838765-A-G, CADD 24.20, PolyPhen-2 0.81
- H58L (p.His58Leu), gnomAD 15-88838765-A-T, CADD 23.00, PolyPhen-2 0.06
- H58Q (p.His58Gln), gnomAD 15-88838766-C-A, CADD 23.00, PolyPhen-2 0.75
- P59R (p.Pro59Arg), gnomAD rs1296607237
- P59H (p.Pro59His), gnomAD 15-88838768-C-A, CADD 23.70, PolyPhen-2 0.96
- P59P (p.Pro59Pro), rs1896571262, gnomAD 15-88838769-T-C, CADD 2.02
- V60L (p.Val60Leu), Ensembl rs902589912
- T61T (p.Thr61Thr), gnomAD 15-88838775-C-T, CADD 7.14
- T62N (p.Thr62Asn), rs200239326, ClinGen CA7719162, ClinVar RCV000294749, ClinVar RCV002518947, CADD 22.40, PolyPhen-2 0.90, Conflicting interpretations, not specified; Inborn genetic diseases; not provided
- T62A (p.Thr62Ala), gnomAD 15-88838776-A-G, CADD 24.00, PolyPhen-2 0.65
- T62T (p.Thr62Thr), gnomAD 15-88838778-C-A, CADD 1.26
- A63D (p.Ala63Asp), rs1245147885, ClinGen CA393714906, ClinVar RCV003340686, NCI-TCGA TCGA novel, AlphaMissense 0.32, MetaLR 0.03, Uncertain significance, Spondyloepimetaphyseal dysplasia, aggrecan type
- A63G (p.Ala63Gly), gnomAD rs1245147885, AlphaMissense 0.32, MetaLR 0.03
- A63P (p.Ala63Pro), rs749720584, ClinGen CA393714904, ClinVar RCV001893533, 1000Genomes rs749720584, AlphaMissense 0.34, MetaLR 0.02, Uncertain significance, not provided
- A63T (p.Ala63Thr), rs749720584, ClinGen CA7719164, NCI-TCGA Cosmic COSV6136, cosmic curated COSV61368, AlphaMissense 0.34, MetaLR 0.02, Uncertain significance, not provided
- P64L (p.Pro64Leu), gnomAD rs1296036330, CADD 20.30, PolyPhen-2 0.99
- P64S (p.Pro64Ser), cosmic curated COSV61362, gnomAD rs1178817726, CADD 23.50, PolyPhen-2 0.99
- P64R (p.Pro64Arg), gnomAD 15-88838783-C-G, CADD 23.60, PolyPhen-2 0.91
- S65P (p.Ser65Pro), TOPMed rs1169765470
- S65Y (p.Ser65Tyr), rs755142678, ClinGen CA7719165, NCI-TCGA Cosmic COSV6135, cosmic curated COSV61357, CADD 22.10, PolyPhen-2 0.88, Uncertain significance, not specified; Inborn genetic diseases; not provided
- p.Ser65 Pro68del, rs771754676, gnomAD 15-88838775-CACCG, CADD 16.70
- S65F (p.Ser65Phe), gnomAD 15-88838779-G-GC, CADD 25.90
- S65S (p.Ser65Ser), rs779210441, gnomAD 15-88838787-T-C, CADD 6.79
- T66I (p.Thr66Ile), ExAC rs748136311, gnomAD rs748136311, CADD 21.60, PolyPhen-2 0.29
- T66T (p.Thr66Thr), rs1448004781, gnomAD 15-88838790-C-T, CADD 0.34
- A67G (p.Ala67Gly), Ensembl rs969717268
- A67S (p.Ala67Ser), 1000Genomes rs182894280, ESP rs182894280, ExAC rs182894280, TOPMed rs182894280, Uncertain significance
- A67T (p.Ala67Thr), rs182894280, ClinGen CA7719168, cosmic curated COSV10071, ClinVar RCV000521389, CADD 20.50, PolyPhen-2 0.25, Conflicting interpretations, not specified; not provided
- A67V (p.Ala67Val), Ensembl rs969717268, CADD 14.70, PolyPhen-2 0.15, Uncertain significance, Inborn genetic diseases
- P68Q (p.Pro68Gln), rs773473572, ClinGen CA7719169, NCI-TCGA Cosmic COSV6135, cosmic curated COSV61358, CADD 23.70, PolyPhen-2 0.98, Uncertain significance, not provided
- P68S (p.Pro68Ser), gnomAD 15-88838794-C-T, CADD 23.30, PolyPhen-2 0.93
- P68P (p.Pro68Pro), rs372041880, gnomAD 15-88838796-A-G, CADD 6.79
- p.Leu69 Pro71del, gnomAD 15-88838790-CGCCC, CADD 17.80
- L69V (p.Leu69Val), gnomAD 15-88838797-C-G, CADD 22.50, PolyPhen-2 0.99
- L69L (p.Leu69Leu), rs1896572854, gnomAD 15-88838797-C-T, CADD 6.13
- A70V (p.Ala70Val), gnomAD 15-88838801-C-T, CADD 22.40, PolyPhen-2 0.03
- P71S (p.Pro71Ser), gnomAD 15-88838803-C-T, CADD 25.10, PolyPhen-2 0.98
- P71R (p.Pro71Arg), gnomAD 15-88838804-C-G, CADD 25.20, PolyPhen-2 0.99
- R72G (p.Arg72Gly), gnomAD rs1443393833, CADD 26.20, PolyPhen-2 0.97
- R72S (p.Arg72Ser), ExAC rs769916642, TOPMed rs769916642, gnomAD rs769916642, CADD 25.00, PolyPhen-2 0.97
- I73V (p.Ile73Val), rs775409722, ClinGen CA7719172, ClinVar RCV003083724, ClinVar RCV005535515, CADD 24.40, PolyPhen-2 0.41, Uncertain significance, Inborn genetic diseases; not provided
- I73I (p.Ile73Ile), rs762816809, gnomAD 15-88838811-C-T, CADD 10.50
- K74R (p.Lys74Arg), NCI-TCGA TCGA novel, gnomAD rs1896573345, CADD 25.50, Variant assessed as somatic; moderate impact.
- K74K (p.Lys74Lys), gnomAD 15-88838814-G-A, CADD 8.84
- W75* (p.Trp75Ter), TOPMed rs1168641758, gnomAD rs1168641758, CADD 44.00
- W75R (p.Trp75Arg), rs1555453695, ClinGen CA393714975, ClinVar RCV001814991, Ensembl rs1555453695, AlphaMissense 1.00, MetaLR 0.91, Pathogenic, Short stature and advanced bone age, with early-onset osteoarthritis
- S76T (p.Ser76Thr), TOPMed rs1399907758, gnomAD rs1399907758, CADD 24.80, PolyPhen-2 0.39, Uncertain significance, Inborn genetic diseases
- S76R (p.Ser76Arg), gnomAD 15-88838820-C-G, CADD 24.20, PolyPhen-2 0.98
- R77C (p.Arg77Cys), rs575468209, ClinGen CA7719174, cosmic curated COSV61355, ClinVar RCV001795710, CADD 23.40, PolyPhen-2 0.03, Uncertain significance, Inborn genetic diseases; not provided
- R77H (p.Arg77His), rs199701329, ClinGen CA7719175, ClinVar RCV000514420, ClinVar RCV000989369, CADD 20.50, PolyPhen-2 0.04, Conflicting interpretations, not provided; Osteochondritis dissecans; Inborn genetic diseases
- R77R (p.Arg77Arg), gnomAD 15-88838823-T-C, CADD 2.07
- V78A (p.Val78Ala), gnomAD rs1403917136, CADD 22.60, PolyPhen-2 0.12
Public ACAN analysis runs
- ACAN analysis run — ACAN (3,035 variants) — completed 2026-08-22