Is TP53 p.Trp53fs (c.158_163delinsAT) pathogenic?

TP53 p.Trp53fs (c.158163delinsAT) is classified Pathogenic in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-19). No gnomAD frequency available for this variant; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with TP53 p.Trp53fs (c.158_163delinsAT)?

TP53 p.Trp53fs (c.158_163delinsAT) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is TP53 p.Trp53fs (c.158_163delinsAT) in the general population?

TP53 p.Trp53fs (c.158_163delinsAT) is no gnomAD frequency available for this variant (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TP53 p.Trp53fs

c.158_163delinsAT · rs2151042609 · VCV1679017

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast ovarian cancer 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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.028	GERP -2.2

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.Trp53fs
Coding: c.158_163delinsAT
MANE Select: NM_000546
dbSNP: rs2151042609
Type: Indel
Location: chr17:7676206 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 53: a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region

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

Disease context

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

TP53 p.Trp53Ter Pathogenic ★ same residue
TP53 p.Trp53Arg Uncertain significance ★ same residue
TP53 p.Trp53Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 p.Arg248Gln Pathogenic ★★★ same condition
TP53 p.Leu194Arg Pathogenic ★★★ same condition
TP53 p.Arg156His Uncertain significance ★★★ ⚠ same condition
TP53 p.Arg158Cys Uncertain significance ★★★ ⚠ 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-trp53fs (accessed [today's date]).

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