# NM_000546.6(TP53):c.844C>T (p.Arg282Trp)

https://sugi.bio/variant/tp53-p-arg282trp

## Summary

**TP53 p.Arg282Trp (c.844C>T)** is classified **Pathogenic/Likely pathogenic** in TP53 (ClinVar, Multiple submitters, 41 submitters; last evaluated 2026-05-29). AlphaMissense: likely pathogenic (0.9462); Very rare (popmax 8.47e-05%, nfe); Associated with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype.

**At a glance:** Pathogenic/Likely pathogenic · review: Multiple submitters · rsID rs28934574 · 41 submitters · 10 linked conditions · AlphaMissense likely pathogenic · very rare (popmax 8.47e-05%, nfe)

## For patients & families {#patients}

This is a change in the TP53 gene that is considered likely disease-causing, submitted by 41 submitters, and is linked to diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Clinical trials | 1 registered for this condition — see ClinicalTrials.gov |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0026635/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TP53](https://sugi.bio/atlas/gene/TP53/) |
| Protein change (HGVS p.) | p.Arg282Trp |
| Coding change (HGVS c.) | c.844C>T |
| MANE Select transcript | [NM_000546](https://www.ncbi.nlm.nih.gov/nuccore/NM_000546) |
| dbSNP | [rs28934574](https://www.ncbi.nlm.nih.gov/snp/rs28934574/) |
| Variant type | single nucleotide variant |
| Location | chr17:7673776-7673776 (GRCh38) |
| ClinVar | [VCV12364](https://www.ncbi.nlm.nih.gov/clinvar/variation/12364/) |

**All HGVS expressions:** `LRG_321:g.18775C>T`, `LRG_321t1:c.844C>T`, `NC_000017.10:g.7577094G>A`, `NC_000017.11:g.7673776G>A`, `NG_017013.2:g.18775C>T`, `NM_000546.5:c.[844C>T]`, `NM_000546.6:c.844C>T`, `NM_001126112.3:c.844C>T`, `NM_001126113.3:c.844C>T`, `NM_001126114.3:c.844C>T`, `NM_001126115.2:c.448C>T`, `NM_001126116.2:c.448C>T`, `NM_001126117.2:c.448C>T`, `NM_001126118.2:c.727C>T`, `NM_001276695.3:c.727C>T`, `NM_001276696.3:c.727C>T`, `NM_001276697.3:c.367C>T`, `NM_001276698.3:c.367C>T`, `NM_001276699.3:c.367C>T`, `NM_001276760.3:c.727C>T`, `NM_001276761.3:c.727C>T`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- AlphaMissense **likely pathogenic** (0.9462) — concordant with the pathogenic call
- REVEL 0.896 (moderately pathogenic-leaning) — agrees with AlphaMissense
- SaProt LLR -14.468 (damaging) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this damaging
- Conservation: phyloP 6.503, GERP -1.2, phastCons 1 — highly conserved (agrees)
- CADD: **PHRED 28.0**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 0.89** across the covering region of the MANE Select transcript (7,669,612–7,676,594), spanning 6,982 bp. Chi-square p 0.0085. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **8.47e-05%** (nfe) · 1/1,180,022 in the highest group · 1/152,016 alleles overall — very rare (popmax 8.47e-05%, nfe).

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**TP53** population constraint: LOEUF 0.449, pLI 0.99798, missense-Z 1.1539; ClinGen dosage — haploinsufficiency 3, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Li-Fraumeni syndrome** — Definitive (AD)

## Protein context {#protein}

Residue **282** lies in a DNA-binding region; the 'interaction with axin1' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with e4f1' region; a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation; does not induce snai1 degradation); the 'disordered' region; an α-helix; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region.

AlphaFold model confidence (whole protein): pLDDT 75.83, 54% of residues very-high.

**321 experimental structure(s)** (PDB): [1A1U](https://www.rcsb.org/structure/1A1U), [1AIE](https://www.rcsb.org/structure/1AIE), [1C26](https://www.rcsb.org/structure/1C26), [1DT7](https://www.rcsb.org/structure/1DT7), [1GZH](https://www.rcsb.org/structure/1GZH), [1H26](https://www.rcsb.org/structure/1H26) — incl. mutant structure 1A1U.

## What this gene does {#gene-function}

*Describes the biological roles of TP53 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** TP53's established molecular role includes transcription cis-regulatory region binding. p.Arg282Trp falls in a DNA-binding region. In Reactome, TP53 is annotated in disease pathway(s) including **Loss of function of TP53 in cancer due to loss of tetramerization ability**, **Signaling by ALK fusions and activated point mutants**.

**Disease mechanism (Reactome):** TP53 loss or alteration is curated in [Loss of function of TP53 in cancer due to loss of tetramerization ability](https://reactome.org/content/detail/R-HSA-9723905), [Signaling by ALK fusions and activated point mutants](https://reactome.org/content/detail/R-HSA-9725370).

### Pathways affected {#pathways}

TP53 participates in **47 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Loss of function of TP53 in cancer due to loss of tetramerization ability](https://reactome.org/content/detail/R-HSA-9723905) | curated |
| ⚕ [Signaling by ALK fusions and activated point mutants](https://reactome.org/content/detail/R-HSA-9725370) | curated |
| [Activation of NOXA and translocation to mitochondria](https://reactome.org/content/detail/R-HSA-111448) | curated |
| [Activation of PUMA and translocation to mitochondria](https://reactome.org/content/detail/R-HSA-139915) | curated |
| [Autodegradation of the E3 ubiquitin ligase COP1](https://reactome.org/content/detail/R-HSA-349425) | curated |
| [DNA Damage/Telomere Stress Induced Senescence](https://reactome.org/content/detail/R-HSA-2559586) | curated |
| [Formation of Senescence-Associated Heterochromatin Foci (SAHF)](https://reactome.org/content/detail/R-HSA-2559584) | curated |
| [G2/M Checkpoints](https://reactome.org/content/detail/R-HSA-69481) | curated |
| [G2/M DNA damage checkpoint](https://reactome.org/content/detail/R-HSA-69473) | curated |
| [Interleukin-4 and Interleukin-13 signaling](https://reactome.org/content/detail/R-HSA-6785807) | curated |
| [Negative transcriptional regulation of urea cycle enzymes](https://reactome.org/content/detail/R-HSA-9988426) | curated |
| [Oncogene Induced Senescence](https://reactome.org/content/detail/R-HSA-2559585) | curated |
| [Ovarian tumor domain proteases](https://reactome.org/content/detail/R-HSA-5689896) | curated |
| [Oxidative Stress Induced Senescence](https://reactome.org/content/detail/R-HSA-2559580) | curated |
| [PI5P Regulates TP53 Acetylation](https://reactome.org/content/detail/R-HSA-6811555) | curated |
| [PKR-mediated signaling](https://reactome.org/content/detail/R-HSA-9833482) | curated |
| [Pre-NOTCH Transcription and Translation](https://reactome.org/content/detail/R-HSA-1912408) | curated |
| [Pyroptosis](https://reactome.org/content/detail/R-HSA-5620971) | curated |
| [RUNX3 regulates CDKN1A transcription](https://reactome.org/content/detail/R-HSA-8941855) | curated |
| [Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks](https://reactome.org/content/detail/R-HSA-5693565) | curated |
| [Regulation of NF-kappa B signaling](https://reactome.org/content/detail/R-HSA-9758274) | curated |
| [Regulation of TP53 Activity through Acetylation](https://reactome.org/content/detail/R-HSA-6804758) | curated |
| [Regulation of TP53 Activity through Association with Co-factors](https://reactome.org/content/detail/R-HSA-6804759) | curated |
| [Regulation of TP53 Activity through Methylation](https://reactome.org/content/detail/R-HSA-6804760) | curated |
| [Regulation of TP53 Activity through Phosphorylation](https://reactome.org/content/detail/R-HSA-6804756) | curated |
| [Regulation of TP53 Degradation](https://reactome.org/content/detail/R-HSA-6804757) | curated |
| [Regulation of TP53 Expression](https://reactome.org/content/detail/R-HSA-6804754) | curated |
| [SUMOylation of transcription factors](https://reactome.org/content/detail/R-HSA-3232118) | curated |
| [Stabilization of p53](https://reactome.org/content/detail/R-HSA-69541) | curated |
| [TP53 Regulates Metabolic Genes](https://reactome.org/content/detail/R-HSA-5628897) | curated |
| [TP53 Regulates Transcription of Caspase Activators and Caspases](https://reactome.org/content/detail/R-HSA-6803207) | curated |
| [TP53 Regulates Transcription of DNA Repair Genes](https://reactome.org/content/detail/R-HSA-6796648) | curated |
| [TP53 Regulates Transcription of Death Receptors and Ligands](https://reactome.org/content/detail/R-HSA-6803211) | curated |
| [TP53 Regulates Transcription of Genes Involved in Cytochrome C Release](https://reactome.org/content/detail/R-HSA-6803204) | curated |
| [TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest](https://reactome.org/content/detail/R-HSA-6804116) | curated |
| [TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest](https://reactome.org/content/detail/R-HSA-6804114) | curated |
| [TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain](https://reactome.org/content/detail/R-HSA-6804115) | curated |
| [TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain](https://reactome.org/content/detail/R-HSA-6803205) | curated |
| [The role of GTSE1 in G2/M progression after G2 checkpoint](https://reactome.org/content/detail/R-HSA-8852276) | curated |
| [Transcriptional  activation of  cell cycle inhibitor p21 ](https://reactome.org/content/detail/R-HSA-69895) | curated |
| [Transcriptional Regulation by VENTX](https://reactome.org/content/detail/R-HSA-8853884) | curated |
| [Ub-specific processing proteases](https://reactome.org/content/detail/R-HSA-5689880) | curated |
| [Association of TriC/CCT with target proteins during biosynthesis](https://reactome.org/content/detail/R-HSA-390471) | electronic |
| [Factors involved in megakaryocyte development and platelet production](https://reactome.org/content/detail/R-HSA-983231) | electronic |
| [Regulation of PTEN gene transcription](https://reactome.org/content/detail/R-HSA-8943724) | electronic |
| [Urea cycle](https://reactome.org/content/detail/R-HSA-70635) | other |
| [Zygotic genome activation (ZGA)](https://reactome.org/content/detail/R-HSA-9819196) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** transcription cis-regulatory region binding, RNA polymerase II cis-regulatory region sequence-specific DNA binding, DNA-binding transcription factor activity, RNA polymerase II-specific, cis-regulatory region sequence-specific DNA binding, core promoter sequence-specific DNA binding, TFIID-class transcription factor complex binding.

**Biological process:** negative regulation of transcription by RNA polymerase II, hematopoietic progenitor cell differentiation, nucleotide-excision repair, regulation of DNA-templated transcription, regulation of transcription by RNA polymerase II, autophagy.

## Clinical significance {#significance}

**Pathogenic/Likely pathogenic** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-05-29.

**Submitter consensus:** conflicting (34 Pathogenic, 5 Likely pathogenic, 1 Likely benign, 1 pathogenic, 1 Likely Pathogenic).

**Submission history:** 53 submissions (1995–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Pathway Genomics | Pathogenic | no assertion criteria provided | clinical testing | 2014-07-24 |
| CSER _CC_NCGL, University of Washington | Likely benign | no assertion criteria provided | research | 2014-06-01 |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 1995-01-01 |
| Illumina Laboratory Services, Illumina | Pathogenic | criteria provided, single submitter | clinical testing | 2017-04-27 |
| Genetic Services Laboratory, University of Chicago | Pathogenic | criteria provided, single submitter | clinical testing | 2018-08-08 |
| BRCAlab, Lund University | Pathogenic | no assertion criteria provided | clinical testing | 2022-08-26 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Pathogenic | criteria provided, single submitter | clinical testing | 2023-12-18 |
| Clinical Genetics and Genomics, Karolinska University Hospital | Pathogenic | no assertion criteria provided | clinical testing | 2024-10-01 |
| Ambry Genetics | Pathogenic | criteria provided, single submitter | clinical testing | 2024-07-05 |
| Color Diagnostics, LLC DBA Color Health | Pathogenic | criteria provided, single submitter | clinical testing | 2024-03-20 |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2026-01-02 |
| Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Pathogenic | criteria provided, single submitter | clinical testing | 2026-02-18 |
| University of Washington Department of Laboratory Medicine, University of Washington | Pathogenic | criteria provided, single submitter | clinical testing | 2015-11-20 |
| GeneKor MSA | Likely pathogenic | criteria provided, single submitter | clinical testing | 2020-01-01 |
| Sema4, Sema4 | Pathogenic | criteria provided, single submitter | curation | 2021-10-31 |
| Genome-Nilou Lab | Likely pathogenic | criteria provided, single submitter | clinical testing | 2022-06-18 |
| Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn | Pathogenic | criteria provided, single submitter | clinical testing | 2022-11-07 |
| Mendelics | Pathogenic | criteria provided, single submitter | clinical testing | 2018-07-02 |
| Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital | Likely pathogenic | criteria provided, single submitter | research | 2019-02-12 |
| KCCC/NGS Laboratory, Kuwait Cancer Control Center | Pathogenic | criteria provided, single submitter | clinical testing | 2023-07-07 |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Pathogenic | criteria provided, single submitter | clinical testing | 2022-11-03 |
| Baylor Genetics | Pathogenic | criteria provided, single submitter | clinical testing | 2024-02-14 |
| All of Us Research Program, National Institutes of Health | Pathogenic | criteria provided, single submitter | clinical testing | 2024-05-14 |
| Center for Personalized Medicine, Children's Hospital Los Angeles | Pathogenic | criteria provided, single submitter | clinical testing | 2018-02-04 |
| St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Pathogenic | criteria provided, single submitter | clinical testing | 2016-11-04 |
| Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo | Pathogenic | criteria provided, single submitter | case-control |  |
| MGZ Medical Genetics Center | Pathogenic | criteria provided, single submitter | clinical testing | 2022-08-08 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2024-02-14 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2024-02-20 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2024-04-11 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2024-06-07 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2024-09-06 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2025-04-04 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2023-02-16 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2023-06-21 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital |  | criteria provided, single submitter | clinical testing | 2023-09-26 |
| Quest Diagnostics Nichols Institute San Juan Capistrano | pathogenic | criteria provided, single submitter | clinical testing | 2025-01-23 |
| Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Pathogenic | criteria provided, single submitter | clinical testing | 2025-02-11 |
| Genetics Laboratory, Great Ormond Street Hospital NHS Foundation Trust, North Thames Genomic Laboratory Hub | Pathogenic | criteria provided, single submitter | clinical testing | 2026-03-10 |
| Dasa | Pathogenic | criteria provided, single submitter | clinical testing | 2025-04-28 |
| Mayo Clinic Laboratories, Mayo Clinic | Pathogenic | no assertion criteria provided | clinical testing |  |
| German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne | Likely pathogenic | no assertion criteria provided | research | 2018-12-01 |
| GeneDx | Pathogenic | criteria provided, single submitter | clinical testing | 2021-05-21 |
| Baylor Genetics | Pathogenic | criteria provided, single submitter | clinical testing | 2021-01-06 |
| Neuberg Centre For Genomic Medicine, NCGM | Pathogenic | criteria provided, single submitter | clinical testing |  |
| Myriad Genetics, Inc. | Pathogenic | criteria provided, single submitter | clinical testing | 2023-04-12 |
| Molecular Diagnostics Laboratory, Catalan Institute of Oncology | Pathogenic | criteria provided, single submitter | clinical testing | 2024-04-19 |
| Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital |  | criteria provided, single submitter | clinical testing | 2025-03-04 |
| Department of Clinical Biochemistry, Naestved Hospital |  | no assertion criteria provided | research | 2024-10-10 |
| Counsyl | Pathogenic | no assertion criteria provided | clinical testing | 2017-04-18 |
| Diller/Parad Lab, Dana-Farber/Harvard Cancer Center | Likely Pathogenic | criteria provided, single submitter | research | 2026-05-29 |

## Associated conditions {#conditions}

[diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype](https://sugi.bio/atlas/disease/diffuse-pediatric-type-high-grade-glioma-h3-wildtype-and-idh-wildtype/), [colorectal cancer](https://sugi.bio/atlas/disease/colorectal-cancer/), [adrenocortical carcinoma, hereditary](https://sugi.bio/atlas/disease/adrenocortical-carcinoma-hereditary/), [head and neck squamous cell carcinoma](https://sugi.bio/atlas/disease/head-and-neck-squamous-cell-carcinoma/), [hereditary neoplastic syndrome](https://sugi.bio/atlas/disease/hereditary-neoplastic-syndrome/), [anaplastic astrocytoma](https://sugi.bio/atlas/disease/anaplastic-astrocytoma/), [pleomorphic xanthoastrocytoma](https://sugi.bio/atlas/disease/pleomorphic-xanthoastrocytoma/), [Li-Fraumeni syndrome](https://sugi.bio/atlas/disease/li-fraumeni-syndrome/), [ovarian neoplasm](https://sugi.bio/atlas/disease/ovarian-neoplasm/), [Li-fraumeni-like syndrome](https://sugi.bio/atlas/disease/li-fraumeni-like-syndrome/).

**Reported phenotype names (ClinVar):** Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, Li-fraumeni-like syndrome, Li-Fraumeni syndrome 1, Li-Fraumeni syndrome, Hereditary cancer-predisposing syndrome, not provided, Squamous cell carcinoma of the head and neck, Astrocytoma, anaplastic, Pleomorphic xanthoastrocytoma, Ovarian neoplasm.

## Same-residue context {#hotspot}

Residue **282** carries **4 other pathogenic ClinVar variants** — a recurrently-mutated position: [TP53 p.Arg282Gly](/variant/tp53-p-arg282gly), [TP53 p.Arg282Pro](/variant/tp53-p-arg282pro), [TP53 p.Arg282fs](/variant/tp53-p-arg282fs), [TP53 p.Arg282_His296del](/variant/tp53-p-arg282-his296del). *Positional co-occurrence of independent ClinVar records, not functional proof.*

## Cancer therapy associations (CIViC) {#civic}

Curated clinical evidence for this variant from CIViC (profile *R282W*):

| Disease | Therapies | Type | Level | Significance |
| --- | --- | --- | --- | --- |
|  |  | Functional | D | Dominant Negative |
|  |  | Functional | D | Neomorphic |
*CIViC evidence levels A–E (A strongest). Therapy associations are context-specific — not a treatment recommendation.*

## Similar variants {#similar}

Related TP53 variant pages (same residue, condition, or type): [TP53 p.Arg282Leu](/variant/tp53-p-arg282leu), [TP53 p.Arg282Gly](/variant/tp53-p-arg282gly), [TP53 p.Arg282Pro](/variant/tp53-p-arg282pro), [TP53 p.Arg282=](/variant/tp53-p-arg282), [TP53 p.Arg282Gln](/variant/tp53-p-arg282gln), [TP53 p.Arg282fs](/variant/tp53-p-arg282fs), [TP53 p.Arg282_Arg283insThr](/variant/tp53-p-arg282-arg283insthr), [TP53 p.Arg282_His296del](/variant/tp53-p-arg282-his296del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 12364). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*