Is TP53 p.Arg280fs (c.837del) pathogenic?

TP53 p.Arg280fs (c.837del) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-02). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Arg280fs (c.837del)?

TP53 p.Arg280fs (c.837del) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Arg280fs (c.837del) in the general population?

TP53 p.Arg280fs (c.837del) is absent from gnomAD (gnomAD).

TP53 p.Arg280fs

c.837del · rs2543542919 · VCV2736412

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TP53
Protein: p.Arg280fs
Coding: c.837del
MANE Select: NM_000546
dbSNP: rs2543542919
Type: Deletion
Location: chr17:7673783 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 280: a DNA-binding region; the 'interaction with axin1' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation; no effect on interaction with ccar2); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with e4f1' region; the 'interaction with dna' 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Arg280del Pathogenic ★ same residue
TP53 p.Arg280Ser Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg280Ter Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg280Thr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg280_Arg283delinsHis Likely pathogenic ★ same residue
TP53 p.Arg280_Arg283delinsSer Uncertain significance ★ same residue
TP53 p.Arg280Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Arg280Ile Conflicting classifications of pathogenicity ★ ⚠ 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-arg280fs (accessed [today's date]).

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