Is TP53 p.Arg282Trp (c.844C>T) pathogenic?

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.

How common is TP53 p.Arg282Trp (c.844C>T) in the general population?

TP53 p.Arg282Trp (c.844C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TP53 p.Arg282Trp (c.844C>T)?

AlphaMissense predicts likely pathogenic (score 0.9462) — an in-silico prediction, not a clinical call.

TP53 p.Arg282Trp

Q: What condition is associated with TP53 p.Arg282Trp (c.844C>T)?

TP53 p.Arg282Trp (c.844C>T) is associated with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, colorectal cancer, adrenocortical carcinoma, hereditary (ClinVar).

c.844C>T · rs28934574 · VCV12364

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 41 submitters

AlphaMissense

likely pathogenic

0.9462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype

Computational evidence

Protein change
AlphaMissense	0.9462	likely pathogenic ✓ concordant with ClinVar
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -14.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 0.000658% 1/152,016 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
		D	Dominant Negative
		D	Neomorphic

Variant & gene context

Gene: TP53
Protein: p.Arg282Trp
Coding: c.844C>T
MANE Select: NM_000546
dbSNP: rs28934574
Type: single nucleotide variant
Location: chr17:7673776 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 282: 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

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer adrenocortical carcinoma, hereditary head and neck squamous cell carcinoma hereditary neoplastic syndrome anaplastic astrocytoma pleomorphic xanthoastrocytoma Li-Fraumeni syndrome ovarian neoplasm Li-fraumeni-like syndrome

Similar variants

TP53 p.Arg282Leu Uncertain significance ★★★ ⚠ same residue
TP53 p.Arg282Gly Pathogenic ★★ same residue
TP53 p.Arg282Pro Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg282= Likely benign ★★ same residue
TP53 p.Arg282Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Arg282fs Pathogenic ★★ same residue
TP53 p.Arg282_Arg283insThr Uncertain significance ★ same residue
TP53 p.Arg282_His296del Likely pathogenic same residue

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tp53-p-arg282trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown