CDKN2A (Tumor suppressor ARF) variants and mutations
CDKN2A (also known as Tumor suppressor ARF) is a human protein-coding gene encoding a tumor suppressor ARF protein. The ARF product of CDKN2A is a tumor-suppressor protein that binds MDM2 and helps preserve p53 activity. By promoting cell-cycle arrest and apoptosis, it provides an important barrier to uncontrolled cell growth from within the nucleolus. This analysis covers 665 CDKN2A variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes melanoma, cutaneous malignant, susceptibility to, 2, familial atypical multiple mole melanoma syndrome, and melanoma. Example CDKN2A variants include M1?, M1I, and M1T.
Variant analysis overview
- Gene: CDKN2A
- Protein: Tumor suppressor ARF
- UniProt accession: Q8N726
- Organism: Homo sapiens
- Variants analyzed: 665
- Variant scope: all variants
- Completed: 2026-07-15
Variant and mutation evidence
- Variant composition: 577 unspecified-consequence records; 7 stop lost; 43 missense variants; 16 synonymous variants; 5 frameshift variants; 4 stop-gained variants; 1 in-frame deletions; 1 stop retained variant; 1 in-frame insertions; 8 substitution
- Prediction scores: 484 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: melanoma, cutaneous malignant, susceptibility to, 2, familial atypical multiple mole melanoma syndrome, melanoma, cutaneous melanoma, melanoma and neural system tumor syndrome, familial melanoma, squamous cell lung carcinoma, head and neck squamous cell carcinoma, cancer, hepatocellular carcinoma, superficial spreading melanoma, neurodegenerative disease.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, PharmGKB, MaveDB, LitVar.
Notable CDKN2A variants
Examples include M1?, M1I, M1T, M1V, V2E, V2L, V2M, R3C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV64270, cosmic curated COSV10746
- M1I (p.Met1Ile), rs1820538211, ClinGen CA373087134, ClinVar RCV001317779, ClinVar RCV005866941, MetaLR 0.33, MetaSVM -0.62, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- M1T (p.Met1Thr), rs759736526, ClinGen CA5012403, ClinVar RCV003387332, ClinVar RCV005871142, MetaLR 0.31, MetaSVM -0.65, Conflicting interpretations, Melanoma-pancreatic cancer syndrome; Hereditary cancer-predisposing syndrome
- M1V (p.Met1Val), rs1820538394, ClinGen CA373087139, ClinVar RCV001050470, ClinVar RCV004609592, MetaLR 0.32, MetaSVM -0.59, Conflicting interpretations, Melanoma-pancreatic cancer syndrome; Familial melanoma; Hereditary cancer-predis
- V2E (p.Val2Glu), rs2489328462, ClinGen CA373087129, ClinVar RCV003306234, Uncertain significance, Hereditary cancer-predisposing syndrome
- V2L (p.Val2Leu), rs1820538120, ClinGen CA373087130, ClinVar RCV001867351, Ensembl rs1820538120, AlphaMissense 0.44, MetaLR 0.20, Uncertain significance, Familial melanoma
- V2M (p.Val2Met), rs1820538120, ClinGen CA373087131, cosmic curated COSV64272, ClinVar RCV001339657, AlphaMissense 0.44, MetaLR 0.20, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R3C (p.Arg3Cys), rs1554659249, ClinGen CA373087124, ClinVar RCV000535941, ClinVar RCV000571830, CADD 26.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- R3H (p.Arg3His), rs1820537912, ClinGen CA373087123, ClinVar RCV001052438, ClinVar RCV003160407, CADD 23.70, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R3S (p.Arg3Ser), rs1554659249, ClinGen CA373087126, ClinVar RCV000689606, Ensembl rs1554659249, CADD 24.50, Uncertain significance, Familial melanoma
- R4K (p.Arg4Lys), rs149063626, ClinGen CA190745949, ClinVar RCV000698196, ClinVar RCV004026435, AlphaMissense 0.41, MetaLR 0.63, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R4M (p.Arg4Met), Ensembl rs149063626, Uncertain significance
- R4W (p.Arg4Trp), gnomAD rs1231812885, CADD 28.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- F5I (p.Phe5Ile), rs776987532, ClinGen CA5012402, ClinVar RCV000409400, ClinVar RCV000638997, CADD 23.60, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Melanoma-pancreatic cance
- F5L (p.Phe5Leu), rs1587358694, ClinGen CA373087109, ClinVar RCV000824401, ClinVar RCV002257993, AlphaMissense 0.88, MetaLR 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Familial melanoma
- F5S (p.Phe5Ser), rs2131149044, ClinGen CA373087111, ClinVar RCV001944389, Ensembl rs2131149044, AlphaMissense 0.42, MetaLR 0.27, Uncertain significance, Familial melanoma
- F5Y (p.Phe5Tyr), rs2131149044, ClinGen CA373087112, ClinVar RCV001931721, ClinVar RCV002388894, AlphaMissense 0.42, MetaLR 0.27, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- L6F (p.Leu6Phe), rs1820537175, cosmic curated COSV10084, ClinGen CA373087103, ClinVar RCV001206405, CADD 25.30, Uncertain significance, Familial melanoma
- L6S (p.Leu6Ser), rs2489328317, ClinGen CA373087105, ClinVar RCV003306229, CADD 26.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- V7A (p.Val7Ala), rs771335991, ClinGen CA5012401, ClinVar RCV002046445, ExAC rs771335991, CADD 26.90, Uncertain significance, Familial melanoma
- V7E (p.Val7Glu), cosmic curated COSV10746
- V7L (p.Val7Leu), cosmic curated COSV10084, AlphaMissense 0.31, MetaLR 0.44
- T8A (p.Thr8Ala), rs1820536864, ClinGen CA373087095, cosmic curated COSV64256, ClinVar RCV001220817, CADD 26.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- T8I (p.Thr8Ile), cosmic curated COSV10606, TOPMed rs1820536698, Uncertain significance, Hereditary cancer-predisposing syndrome
- T8N (p.Thr8Asn), rs1820536698, ClinGen CA373087093, ClinVar RCV001284612, ClinVar RCV003382496, CADD 24.70, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- T8S (p.Thr8Ser), rs1820536864, ClinGen CA373087094, ClinVar RCV001246305, ClinVar RCV005532900, CADD 24.60, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- L9H (p.Leu9His), TOPMed rs876659353, gnomAD rs876659353, CADD 25.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- L9P (p.Leu9Pro), rs876659353, ClinGen CA10578855, cosmic curated COSV10084, ClinVar RCV000222350, CADD 25.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- R10G (p.Arg10Gly), rs1554659242, ClinGen CA373087085, ClinVar RCV000638959, ClinVar RCV004025536, CADD 24.30, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- R10P (p.Arg10Pro), Ensembl rs2131148973, Uncertain significance
- R10Q (p.Arg10Gln), rs2131148973, ClinGen CA373087083, cosmic curated COSV10652, ClinVar RCV001776838, AlphaMissense 0.37, MetaLR 0.77, Uncertain significance, not provided
- R10W (p.Arg10Trp), rs1554659242, ClinGen CA373087084, ClinVar RCV002438041, CADD 25.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- I11F (p.Ile11Phe), Ensembl rs1820535855
- I11L (p.Ile11Leu), Ensembl rs1820535855, Uncertain significance, Hereditary cancer-predisposing syndrome
- I11S (p.Ile11Ser), rs1820535713, ClinGen CA373087077, ClinVar RCV001990203, Ensembl rs1820535713, AlphaMissense 0.87, MetaLR 0.58, Uncertain significance, Familial melanoma
- I11T (p.Ile11Thr), rs1820535713, ClinGen CA373087075, ClinVar RCV002326215, AlphaMissense 0.87, MetaLR 0.58, Uncertain significance, Hereditary cancer-predisposing syndrome
- I11V (p.Ile11Val), Ensembl rs1820535855
- R12G (p.Arg12Gly), rs1587358659, ClinGen CA373087073, cosmic curated COSV64261, ClinVar RCV001020459, AlphaMissense 0.35, MetaLR 0.25, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R12Q (p.Arg12Gln), rs201877069, ClinGen CA190745938, cosmic curated COSV64262, ClinVar RCV000709077, CADD 21.30, Uncertain significance, Melanoma and neural system tumor syndrome; Familial melanoma; Melanoma, cutaneou
- R12W (p.Arg12Trp), rs1587358659, ClinGen CA373087072, cosmic curated COSV64268, ClinVar RCV003306233, AlphaMissense 0.35, MetaLR 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome
- R13C (p.Arg13Cys), rs1389587108, ClinGen CA373087067, ClinVar RCV001323248, ClinVar RCV003382523, AlphaMissense 0.43, MetaLR 0.71, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- R13H (p.Arg13His), rs1820535235, cosmic curated COSV10084, ClinVar RCV004575560, TOPMed rs1820535235, AlphaMissense 0.35, MetaLR 0.69, Uncertain significance, Melanoma and neural system tumor syndrome
- R13P (p.Arg13Pro), TOPMed rs1820535235, Uncertain significance
- R13S (p.Arg13Ser), rs1389587108, ClinGen CA373087069, ClinVar RCV004522566, AlphaMissense 0.43, MetaLR 0.71, Uncertain significance, Hereditary cancer-predisposing syndrome
- A14P (p.Ala14Pro), rs1241364288, ClinGen CA373087062, ClinVar RCV001316894, ClinVar RCV004609756, AlphaMissense 0.11, MetaLR 0.24, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- A14T (p.Ala14Thr), rs1241364288, ClinGen CA373087061, cosmic curated COSV64258, ClinVar RCV000687115, AlphaMissense 0.11, MetaLR 0.24, Conflicting interpretations, Familial melanoma; Melanoma-pancreatic cancer syndrome; Melanoma, cutaneous mali
- A14V (p.Ala14Val), cosmic curated COSV64261, Ensembl rs2131148906
- C15G (p.Cys15Gly), TOPMed rs1554659236, Uncertain significance
- C15R (p.Cys15Arg), rs1554659236, ClinGen CA373087056, ClinVar RCV000662739, ClinVar RCV001022430, CADD 2.38, Uncertain significance, Melanoma-pancreatic cancer syndrome; Familial melanoma; Hereditary cancer-predis
- G16C (p.Gly16Cys), ExAC rs773459232, gnomAD rs773459232, AlphaMissense 0.46, MetaLR 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- G16D (p.Gly16Asp), rs1444669684, ClinGen CA373087046, ClinVar RCV001978175, ClinVar RCV002331575, AlphaMissense 0.27, MetaLR 0.36, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- G16R (p.Gly16Arg), rs773459232, ClinGen CA373087049, ClinVar RCV001927356, ClinVar RCV002334828, AlphaMissense 0.46, MetaLR 0.11, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- G16S (p.Gly16Ser), rs773459232, ClinGen CA5012399, cosmic curated COSV10084, ClinVar RCV001062337, AlphaMissense 0.46, MetaLR 0.11, Conflicting interpretations, Familial melanoma; Hereditary cancer-predisposing syndrome; not specified
- G16V (p.Gly16Val), rs1444669684, ClinGen CA373087045, ClinVar RCV000686282, TOPMed rs1444669684, AlphaMissense 0.45, MetaLR 0.45, Uncertain significance, Familial melanoma
- P17L (p.Pro17Leu), rs1820534329, ClinGen CA373087040, cosmic curated COSV10652, ClinVar RCV001210153, AlphaMissense 0.30, MetaLR 0.60, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- P17Q (p.Pro17Gln), rs1820534329, ClinGen CA373087042, ClinVar RCV001214847, Ensembl rs1820534329, AlphaMissense 0.30, MetaLR 0.60, Uncertain significance, Familial melanoma
- P17S (p.Pro17Ser), rs3731190, ClinGen CA5012398, ClinVar RCV000811616, ClinVar RCV003166306, CADD 22.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma; Melanoma and neural
- P18L (p.Pro18Leu), rs1587358603, ClinGen CA373087034, cosmic curated COSV64267, ClinVar RCV001299762, AlphaMissense 0.22, MetaLR 0.29, Uncertain significance, not provided; Familial melanoma; Hereditary cancer-predisposing syndrome
- P18Q (p.Pro18Gln), rs1587358603, ClinGen CA373087036, ClinVar RCV000822783, ClinVar RCV002345907, AlphaMissense 0.27, MetaLR 0.29, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- P18R (p.Pro18Arg), rs1587358603, ClinGen CA373087035, ClinVar RCV001924183, ClinVar RCV002344060, AlphaMissense 0.14, MetaLR 0.29, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R19* (p.Arg19Ter), rs2131148812, ClinGen CA373087033, cosmic curated COSV64268, ClinVar RCV001992217, CADD 35.00, Likely pathogenic
- R19L (p.Arg19Leu), rs748616717, ClinGen CA5012397, ClinVar RCV000479028, ClinVar RCV001320487, AlphaMissense 0.38, MetaLR 0.42, Uncertain significance, Familial melanoma; not provided; Hereditary cancer-predisposing syndrome
- R19P (p.Arg19Pro), rs748616717, ClinGen CA373087030, cosmic curated COSV10527, ClinVar RCV002347559, AlphaMissense 0.38, MetaLR 0.42, Uncertain significance, Hereditary cancer-predisposing syndrome
- R19Q (p.Arg19Gln), rs748616717, ClinGen CA373087031, ClinVar RCV000795505, ClinVar RCV001024429, AlphaMissense 0.38, MetaLR 0.42, Uncertain significance, Familial melanoma; not provided; Hereditary cancer-predisposing syndrome
- V20G (p.Val20Gly), Ensembl rs2131148791
- V20M (p.Val20Met), TOPMed rs1820533989, gnomAD rs1820533989, CADD 23.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- R21E (p.Arg21Glu), rs2489327871, ClinGen CA2580080301, ClinVar RCV002360176, Uncertain significance, Hereditary cancer-predisposing syndrome
- R21G (p.Arg21Gly), TOPMed rs1397255688, gnomAD rs1397255688, CADD 17.70, Uncertain significance
- R21K (p.Arg21Lys), rs1057517601, ClinGen CA16042111, ClinVar RCV000409123, ClinVar RCV000543250, CADD 23.00, Uncertain significance, Melanoma-pancreatic cancer syndrome; Familial melanoma; Hereditary cancer-predis
- R21W (p.Arg21Trp), TOPMed rs1397255688, gnomAD rs1397255688, Uncertain significance, Hereditary cancer-predisposing syndrome
- V22F (p.Val22Phe), Ensembl rs2131148763, AlphaMissense 0.77, MetaLR 0.69
- V22G (p.Val22Gly), Ensembl rs2131148758
- F23L (p.Phe23Leu), rs374360796, ClinGen CA5012396, ClinVar RCV000411867, ClinVar RCV002365449, CADD 25.10, Uncertain significance, Melanoma-pancreatic cancer syndrome; Hereditary cancer-predisposing syndrome
- F23S (p.Phe23Ser), cosmic curated COSV10970
- V24A (p.Val24Ala), rs749723804, ClinGen CA5012395, ClinVar RCV001937831, ClinVar RCV006392229, CADD 22.40, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- V24L (p.Val24Leu), TOPMed rs1406669428, gnomAD rs1406669428, CADD 19.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- V24M (p.Val24Met), rs1406669428, ClinGen CA373087004, ClinVar RCV001283959, TOPMed rs1406669428, CADD 24.00, Uncertain significance, not provided
- V25G (p.Val25Gly), Ensembl rs2131148712, REVEL 0.51, CADD 8.11
- V25I (p.Val25Ile), Ensembl rs2131148720, REVEL 0.16, CADD 16.70, Uncertain significance, Familial melanoma
- H26R (p.His26Arg), rs780803896, ClinGen CA5012394, ClinVar RCV001934651, ClinVar RCV002406945, CADD 14.30, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; Melanoma and neural
- H26Y (p.His26Tyr), rs1820533255, ClinGen CA373086991, cosmic curated COSV64253, ClinVar RCV001225857, AlphaMissense 0.24, MetaLR 0.21, Uncertain significance, Familial melanoma
- I27L (p.Ile27Leu), rs1057517575, ClinGen CA16042110, ClinVar RCV000412466, ClinVar RCV000819361, AlphaMissense 0.47, MetaLR 0.19, Uncertain significance, Melanoma-pancreatic cancer syndrome; Melanoma, cutaneous malignant, susceptibili
- I27M (p.Ile27Met), rs1413839473, ClinGen CA373086981, ClinVar RCV001315519, ClinVar RCV004609751, CADD 22.60, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- I27S (p.Ile27Ser), cosmic curated COSV64263
- I27V (p.Ile27Val), rs1057517575, ClinGen CA373086986, ClinVar RCV002419133, TOPMed rs1057517575, AlphaMissense 0.47, MetaLR 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome
- P28L (p.Pro28Leu), rs1282190742, ClinGen CA373086975, cosmic curated COSV10592, ClinVar RCV001931211, AlphaMissense 0.20, MetaLR 0.23, Conflicting interpretations, Familial melanoma; Hereditary cancer-predisposing syndrome
- P28R (p.Pro28Arg), rs1282190742, ClinGen CA373086977, ClinVar RCV001211113, gnomAD rs1282190742, AlphaMissense 0.20, MetaLR 0.23, Uncertain significance, Familial melanoma
- P28S (p.Pro28Ser), rs1587358521, ClinGen CA373086978, cosmic curated COSV64259, ClinVar RCV000818072, AlphaMissense 0.19, MetaLR 0.18, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- R29L (p.Arg29Leu), gnomAD rs1307839309, CADD 25.40, Uncertain significance, Hereditary cancer-predisposing syndrome
- R29W (p.Arg29Trp), rs1316222103, ClinGen CA373086973, ClinVar RCV000556570, ClinVar RCV002448676, REVEL 0.62, CADD 27.20, Uncertain significance, Melanoma and neural system tumor syndrome; Familial melanoma; Hereditary cancer
- L30F (p.Leu30Phe), rs2131148620, ClinGen CA373086967, ClinVar RCV001875574, ClinVar RCV002370449, CADD 21.70, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- L30P (p.Leu30Pro), Ensembl rs2131148615
- T31A (p.Thr31Ala), rs2131148604, ClinGen CA373086963, cosmic curated COSV10943, ClinVar RCV004522568, AlphaMissense 0.05, MetaLR 0.11, Likely benign, Hereditary cancer-predisposing syndrome
- T31M (p.Thr31Met), rs528789830, ClinGen CA10578853, ClinVar RCV000220549, ClinVar RCV000507625, CADD 22.50, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Familial melanoma; not specified
- T31R (p.Thr31Arg), rs528789830, ClinGen CA5012391, ClinVar RCV000255508, ClinVar RCV000535017, CADD 18.90, Conflicting interpretations, Melanoma-pancreatic cancer syndrome; Hereditary cancer-predisposing syndrome; no
- G32E (p.Gly32Glu), rs370655358, ClinGen CA373086957, ClinVar RCV000561690, ClinVar RCV001217808, AlphaMissense 0.18, MetaLR 0.30, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- G32R (p.Gly32Arg), rs879254043, ClinGen CA10584303, ClinVar RCV000237047, ClinVar RCV000638972, CADD 9.99, Uncertain significance, Familial melanoma
- G32V (p.Gly32Val), cosmic curated COSV64256, ESP rs370655358, ExAC rs370655358, gnomAD rs370655358, AlphaMissense 0.32, MetaLR 0.36, Uncertain significance
- E33* (p.Glu33Ter), rs1287464120, ClinGen CA373086953, ClinVar RCV000705257, TOPMed rs1287464120, CADD 35.00, Pathogenic
- E33G (p.Glu33Gly), rs1820531368, ClinGen CA373086950, cosmic curated COSV64255, ClinVar RCV001315687, AlphaMissense 0.26, MetaLR 0.38, Uncertain significance, Familial melanoma
- E33K (p.Glu33Lys), rs1287464120, ClinGen CA373086955, ClinVar RCV001218136, ClinVar RCV002375193, CADD 24.10, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- W34* (p.Trp34Ter), rs1820531050, cosmic curated COSV10527, ClinGen CA373086943, ClinVar RCV001090490, Pathogenic
- W34G (p.Trp34Gly), rs765285880, ClinGen CA5012387, cosmic curated COSV64261, ClinVar RCV001948181, CADD 17.10, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- W34L (p.Trp34Leu), rs2489327475, ClinGen CA373086946, ClinVar RCV002378191, Uncertain significance, Hereditary cancer-predisposing syndrome
- W34R (p.Trp34Arg), ExAC rs765285880, TOPMed rs765285880, gnomAD rs765285880, CADD 15.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- W34X, rs876658556, Pathogenic
- A35E (p.Ala35Glu), Ensembl rs2131148491, CADD 21.70, Uncertain significance
- A35G (p.Ala35Gly), Ensembl rs2131148491, Uncertain significance, Hereditary cancer-predisposing syndrome
- A35P (p.Ala35Pro), rs1473253589, ClinGen CA373086939, ClinVar RCV001981497, gnomAD rs1473253589, AlphaMissense 0.21, MetaLR 0.26, Uncertain significance, Familial melanoma
- A35S (p.Ala35Ser), rs1473253589, ClinGen CA373086938, ClinVar RCV002389690, AlphaMissense 0.61, MetaLR 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Melanoma and neural syste
- A35T (p.Ala35Thr), gnomAD rs1473253589, AlphaMissense 0.21, MetaLR 0.26, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- A35V (p.Ala35Val), rs2131148491, ClinGen CA373086935, ClinVar RCV001901981, Ensembl rs2131148491, CADD 23.60, Uncertain significance, Familial melanoma
- A36E (p.Ala36Glu), rs1396662899, ClinGen CA373086931, ClinVar RCV002424240, gnomAD rs1396662899, CADD 14.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- A36P (p.Ala36Pro), rs1587358428, ClinGen CA373086933, ClinVar RCV000802091, Ensembl rs1587358428, REVEL 0.70, CADD 24.80, Uncertain significance, Familial melanoma
- A36R (p.Ala36Arg), rs2489327427, ClinGen CA2580616160, ClinVar RCV003316927, Pathogenic
- A36V (p.Ala36Val), rs1396662899, ClinGen CA373086929, ClinVar RCV001224681, gnomAD rs1396662899, REVEL 0.36, CADD 14.40, Uncertain significance, Familial melanoma
- P37A (p.Pro37Ala), rs2131148448, ClinGen CA373086927, ClinVar RCV002258451, Ensembl rs2131148448, AlphaMissense 0.07, MetaLR 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome
- P37L (p.Pro37Leu), rs1361441265, ClinGen CA373086923, ClinVar RCV004522558, gnomAD rs1361441265, AlphaMissense 0.17, MetaLR 0.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- P37R (p.Pro37Arg), rs1361441265, ClinGen CA373086924, ClinVar RCV001347786, ClinVar RCV004951579, AlphaMissense 0.17, MetaLR 0.30, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- G38A (p.Gly38Ala), rs1563902798, ClinGen CA373086918, ClinVar RCV002451893, AlphaMissense 0.21, MetaLR 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome
- G38E (p.Gly38Glu), rs1563902798, ClinGen CA373086919, ClinVar RCV000702320, ClinVar RCV005791927, AlphaMissense 0.22, MetaLR 0.19, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- G38R (p.Gly38Arg), rs1346248530, ClinGen CA373086920, ClinVar RCV001207337, ClinVar RCV002322017, AlphaMissense 0.22, MetaLR 0.19, Uncertain significance, Familial melanoma
- G38V (p.Gly38Val), rs1563902798, ClinGen CA373086917, ClinVar RCV003306232, AlphaMissense 0.34, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome
- G38W (p.Gly38Trp), TOPMed rs1346248530, gnomAD rs1346248530, AlphaMissense 0.22, MetaLR 0.19, Uncertain significance
- A39T (p.Ala39Thr), rs1064795551, ClinGen CA16618841, ClinVar RCV000480619, ClinVar RCV000638956, CADD 6.25, Conflicting interpretations, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- A39V (p.Ala39Val), Ensembl rs2131148392, CADD 3.25
- P40L (p.Pro40Leu), rs1587358382, ClinGen CA373086906, ClinVar RCV000802445, ClinVar RCV005532763, AlphaMissense 0.10, MetaLR 0.09, Conflicting interpretations, Familial melanoma; Hereditary cancer-predisposing syndrome
- P40R (p.Pro40Arg), Ensembl rs1587358382, Uncertain significance
- A41P (p.Ala41Pro), TOPMed rs1064793582, gnomAD rs1064793582, CADD 22.80, Uncertain significance
- A41T (p.Ala41Thr), rs1064793582, ClinGen CA16618840, ClinVar RCV000483036, ClinVar RCV000547575, CADD 22.40, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- A41V (p.Ala41Val), rs2131148341, ClinGen CA373086901, cosmic curated COSV10527, ClinVar RCV003387333, AlphaMissense 0.18, MetaLR 0.46, Uncertain significance, Hereditary cancer-predisposing syndrome
- A42P (p.Ala42Pro), TOPMed rs905621048, Uncertain significance
- A42S (p.Ala42Ser), rs905621048, ClinGen CA373086899, ClinVar RCV001010541, ClinVar RCV001862770, AlphaMissense 0.20, MetaLR 0.22, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- A42T (p.Ala42Thr), rs905621048, ClinGen CA190745885, ClinVar RCV001894313, ClinVar RCV002397792, AlphaMissense 0.20, MetaLR 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- A42V (p.Ala42Val), rs2489327235, ClinGen CA373086896, ClinVar RCV003306227, Uncertain significance, Hereditary cancer-predisposing syndrome
- V43A (p.Val43Ala), rs2131148286, ClinGen CA373086891, ClinVar RCV001959463, Ensembl rs2131148286, AlphaMissense 0.13, MetaLR 0.19, Uncertain significance, Familial melanoma
- V43L (p.Val43Leu), rs1820529552, ClinGen CA373086893, ClinVar RCV001233306, ClinVar RCV002379888, AlphaMissense 0.25, MetaLR 0.31, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- A44S (p.Ala44Ser), rs2489327173, ClinGen CA373086887, ClinVar RCV002385419, Uncertain significance, Hereditary cancer-predisposing syndrome
- A44T (p.Ala44Thr), rs2489327173, ClinGen CA373086888, ClinVar RCV004522560, CADD 18.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- A44V (p.Ala44Val), rs1261184323, ClinGen CA16622046, ClinVar RCV000527714, ClinVar RCV001576781, CADD 18.10, Uncertain significance, Familial melanoma; not provided; Hereditary cancer-predisposing syndrome
- L45F (p.Leu45Phe), TOPMed rs1554659193, gnomAD rs1554659193, CADD 25.80, Uncertain significance
- L45I (p.Leu45Ile), rs1554659193, ClinGen CA373086884, ClinVar RCV001344836, TOPMed rs1554659193, CADD 25.10, Uncertain significance, Familial melanoma
- L45V (p.Leu45Val), rs1554659193, ClinGen CA373086883, ClinVar RCV000563932, ClinVar RCV001318514, CADD 24.90, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; Melanoma and neural
- V46G (p.Val46Gly), rs2489327109, ClinGen CA373086874, ClinVar RCV004522561, Uncertain significance, Hereditary cancer-predisposing syndrome
- V46L (p.Val46Leu), rs786203467, ClinGen CA373086878, ClinVar RCV002042028, TOPMed rs786203467, AlphaMissense 0.48, MetaLR 0.44, Uncertain significance, Familial melanoma
- V46M (p.Val46Met), rs786203467, ClinGen CA196724, ClinVar RCV000166784, ClinVar RCV001065923, AlphaMissense 0.48, MetaLR 0.44, Uncertain significance, Melanoma and neural system tumor syndrome; Melanoma-pancreatic cancer syndrome
- V46X, rs878853644, Likely pathogenic
- L47P (p.Leu47Pro), rs2131148222, ClinGen CA373086870, ClinVar RCV002040764, ClinVar RCV003229080, AlphaMissense 0.56, MetaLR 0.75, Uncertain significance, Familial melanoma; not provided; Hereditary cancer-predisposing syndrome
- M48I (p.Met48Ile), rs1820528469, ClinGen CA373086861, ClinVar RCV001219780, Ensembl rs1820528469, CADD 21.90, Uncertain significance, Hereditary cancer-predisposing syndrome
- M48L (p.Met48Leu), rs1820528622, ClinGen CA373086868, ClinVar RCV004522562, Ensembl rs1820528622, CADD 18.40, Uncertain significance, Hereditary cancer-predisposing syndrome
- M48T (p.Met48Thr), gnomAD rs1357555009, CADD 20.50
- L49P (p.Leu49Pro), rs2489327023, ClinGen CA373086856, ClinVar RCV002396910, ClinVar RCV004697224, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- L49V (p.Leu49Val), rs1554659187, ClinGen CA373086858, ClinVar RCV004522564, CADD 24.70, Uncertain significance, Hereditary cancer-predisposing syndrome
- L50P (p.Leu50Pro), rs1554659181, ClinGen CA373086852, ClinVar RCV002389883, cosmic curated COSV10652, AlphaMissense 0.26, MetaLR 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome
- L50R (p.Leu50Arg), rs1554659181, ClinGen CA373086850, ClinVar RCV000638974, ClinVar RCV001775936, AlphaMissense 0.26, MetaLR 0.22, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- R51K (p.Arg51Lys), rs1014358179, cosmic curated COSV10606, ClinGen CA373086847, ClinVar RCV002402944, AlphaMissense 0.63, MetaLR 0.76, Uncertain significance, Hereditary cancer-predisposing syndrome
- R51T (p.Arg51Thr), rs1014358179, ClinGen CA190745873, ClinVar RCV000560036, ClinVar RCV000570741, AlphaMissense 0.63, MetaLR 0.76, Conflicting interpretations, Familial melanoma; not provided; Hereditary cancer-predisposing syndrome
- S52G (p.Ser52Gly), rs1587358275, ClinGen CA373086842, ClinVar RCV000807404, ClinVar RCV002397651, AlphaMissense 0.19, MetaLR 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- S52N (p.Ser52Asn), rs2489326979, ClinVar RCV004575555, Uncertain significance, Hereditary cancer-predisposing syndrome; Melanoma and neural system tumor syndro
- S52R (p.Ser52Arg), rs2489326972, ClinGen CA373086836, ClinVar RCV003306231, CADD 14.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- S52I (p.Ser52Ile), rs104894109, ClinGen CA120412, ClinVar RCV000010032, ClinVar RCV000471463, REVEL 0.46, CADD 23.40, Pathogenic/Likely pathogenic, not provided; Melanoma-pancreatic cancer syndrome; Melanoma, cutaneous malignant
- Q53P (p.Gln53Pro), ExAC rs772048734, gnomAD rs772048734, CADD 16.60, Uncertain significance
- Q53R (p.Gln53Arg), rs772048734, ClinGen CA5012380, cosmic curated COSV10819, ClinVar RCV000804663, CADD 6.71, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- R54C (p.Arg54Cys), rs896054565, ClinGen CA373086827, ClinVar RCV001068140, ClinVar RCV002393328, CADD 24.30, Uncertain significance, Melanoma and neural system tumor syndrome; Familial melanoma; Hereditary cancer
- R54H (p.Arg54His), rs1587358254, ClinGen CA373086826, ClinVar RCV000022944, ClinVar RCV002399333, AlphaMissense 0.17, MetaLR 0.77, Uncertain significance, Hereditary cancer-predisposing syndrome
- R54S (p.Arg54Ser), rs896054565, ClinGen CA190745865, cosmic curated COSV10592, ClinVar RCV000571273, CADD 18.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma; not provided
- L55P (p.Leu55Pro), cosmic curated COSV64262
- L55V (p.Leu55Val), rs1820527497, ClinGen CA373086823, ClinVar RCV001225219, ClinVar RCV002402706, CADD 6.71, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Familial melanoma
- G56E (p.Gly56Glu), rs748327367, ClinGen CA5012379, ClinVar RCV000542585, ClinVar RCV000566041, AlphaMissense 0.25, MetaLR 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome; Melanoma and neural system tumor syndro
- G56R (p.Gly56Arg), rs1820527345, ClinGen CA373086818, ClinVar RCV001212379, ClinVar RCV002402629, AlphaMissense 0.25, MetaLR 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- Q57H (p.Gln57His), rs1391696399, ClinGen CA373086808, ClinVar RCV003306230, CADD 20.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q57R (p.Gln57Arg), rs774711850, ClinGen CA5012378, ClinVar RCV000482570, ClinVar RCV000563903, CADD 14.50, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome; not provided
- Q58* (p.Gln58Ter), rs2131148082, ClinGen CA373086804, cosmic curated COSV10527, ClinVar RCV001368663, CADD 37.00, Likely pathogenic
- Q58H (p.Gln58His), Ensembl rs2131148077
- Q58R (p.Gln58Arg), rs2489326851, ClinGen CA373086801, ClinVar RCV002399301, ClinVar RCV003228079, CADD 19.50, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P59L (p.Pro59Leu), rs1477583857, ClinGen CA373086794, cosmic curated COSV10527, ClinVar RCV001239844, AlphaMissense 0.16, MetaLR 0.31, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial melanoma
- P59S (p.Pro59Ser), Ensembl rs2131148065
- L60F (p.Leu60Phe), rs769257927, ClinGen CA5012377, ClinVar RCV000638981, ClinVar RCV005231213, CADD 22.60, Uncertain significance, Familial melanoma; not specified; Hereditary cancer-predisposing syndrome
- L60I (p.Leu60Ile), rs769257927, ClinGen CA373086792, ClinVar RCV001304924, ClinVar RCV002411974, CADD 22.40, Uncertain significance, Familial melanoma; Hereditary cancer-predisposing syndrome
- P61L (p.Pro61Leu), rs1820526529, ClinGen CA373086782, ClinVar RCV001365500, Ensembl rs1820526529, AlphaMissense 0.17, MetaLR 0.27, Uncertain significance, Familial melanoma
Public CDKN2A analysis runs
- CDKN2A analysis run — CDKN2A (665 variants) — completed 2026-07-15