Is TP53 p.Lys120Ter (c.358A>T) pathogenic?

TP53 p.Lys120Ter (c.358A>T) is classified Pathogenic in TP53 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-31). No allele count reported in gnomAD v4.1 (AN 1,612,268); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Lys120Ter (c.358A>T)?

TP53 p.Lys120Ter (c.358A>T) is associated with hereditary neoplastic syndrome, Li-fraumeni-like syndrome (ClinVar).

How common is TP53 p.Lys120Ter (c.358A>T) in the general population?

TP53 p.Lys120Ter (c.358A>T) is no allele count reported in gnomAD v4.1 (AN 1,612,268) (gnomAD).

TP53 p.Lys120Ter

c.358A>T · rs121912658 · VCV12363

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,268)

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 4 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Overall
CADD	38.0	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

No allele count reported in gnomAD v4.1 (AN 1,612,268). 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.Lys120Ter
Coding: c.358A>T
MANE Select: NM_000546
dbSNP: rs121912658
Type: single nucleotide variant
Location: chr17:7676011 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 120: a DNA-binding region; the 'interaction with axin1' region; a β-strand; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation; abolished acetylation; impaired ability to induce proapoptotic program; mimics lactylation, leading to decreased ability to undergo liquid-liquid phase separation and activate the transcription factor activity); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation; mimics lactylation, leading to decreased ability to undergo liquid-liquid phase separation and activate the transcription factor activity); a functional site (interaction with dna); a modified residue (n6-acetyllysine); a modified residue (n6-lactoyllysine); 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-like syndrome

Similar variants

TP53 p.Lys120Arg Uncertain significance ★★ ⚠ same residue
TP53 p.Lys120Gln Uncertain significance ★★ ⚠ same residue
TP53 p.Lys120Met Uncertain significance ★★ ⚠ same residue
TP53 p.Lys120Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Lys120= Likely benign ★ same residue
TP53 p.Lys120fs Pathogenic ★ same residue
TP53 p.Lys120Thr Uncertain significance ★ ⚠ same residue
TP53 c.375+5G>A 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-lys120ter (accessed [today's date]).

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