Is TP53 p.Gln52Ter (c.154C>T) pathogenic?

TP53 p.Gln52Ter (c.154C>T) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-17). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Gln52Ter (c.154C>T)?

TP53 p.Gln52Ter (c.154C>T) is associated with Li-Fraumeni syndrome 1, hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Gln52Ter (c.154C>T) in the general population?

TP53 p.Gln52Ter (c.154C>T) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Gln52Ter

c.154C>T · rs2151042795 · VCV1455400

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Li-Fraumeni syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -3.5
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53
Protein: p.Gln52Ter
Coding: c.154C>T
MANE Select: NM_000546
dbSNP: rs2151042795
Type: single nucleotide variant
Location: chr17:7676215 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 52: 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

Li-Fraumeni syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome Li-Fraumeni syndrome

Similar variants

TP53 p.Gln52Arg Uncertain significance ★★ ⚠ same residue
TP53 p.Gln52fs Pathogenic ★ same residue
TP53 p.Gln52= Likely benign ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>A Pathogenic ★★★ same condition
TP53 p.Ala138Pro Likely pathogenic ★★★ same condition
TP53 p.Ala138Val 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-gln52ter (accessed [today's date]).

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