Is TP53 p.Leu289fs (c.864dup) pathogenic?

TP53 p.Leu289fs (c.864dup) is classified Pathogenic in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-23). Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Leu289fs (c.864dup)?

TP53 p.Leu289fs (c.864dup) is associated with hereditary neoplastic syndrome (ClinVar).

TP53 p.Leu289fs

c.864dup · VCV4189272

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 3.6	GERP -3.4, phastCons 1

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

Variant & gene context

Gene: TP53
Protein: p.Leu289fs
Coding: c.864dup
MANE Select: NM_000546
Type: Duplication
Location: chr17:7673755 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 289: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with e4f1' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); 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

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

Similar variants

TP53 p.Leu289= Benign/Likely benign ★★ same residue
TP53 p.Leu289Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Leu289Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Leu289Val Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ter394LeuextTer? Likely pathogenic ★★★ same condition
TP53 p.Leu289Pro Likely benign ★★★ same residue
TP53 c.375+1dup Pathogenic/Likely pathogenic ★★ same condition
TP53 c.97-1_102dup Pathogenic/Likely pathogenic ★★ same condition

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-leu289fs (accessed [today's date]).

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