Is TP53 p.Lys132Ter (c.394A>T) pathogenic?

TP53 p.Lys132Ter (c.394A>T) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-21). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Lys132Ter (c.394A>T)?

TP53 p.Lys132Ter (c.394A>T) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Lys132Ter (c.394A>T) in the general population?

TP53 p.Lys132Ter (c.394A>T) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Lys132Ter

c.394A>T · rs747342068 · VCV2011699

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 5 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Overall
CADD	40.0	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.Lys132Ter
Coding: c.394A>T
MANE Select: NM_000546
dbSNP: rs747342068
Type: single nucleotide variant
Location: chr17:7675218 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 132: a DNA-binding region; the 'interaction with axin1' region; a β-strand; the 'interaction with ccar2' region; a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); 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; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' 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.Lys132Asn Pathogenic ★★★ same residue
TP53 p.Lys132Arg Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Lys132Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Lys132Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Lys132Met Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Lys132Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Lys132fs Pathogenic ★ same residue
TP53 p.Lys132_Met133insLeuAsnLys Uncertain significance ★ 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-lys132ter (accessed [today's date]).

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