Is TP53 p.Arg342Ter (c.1024C>T) pathogenic?

TP53 p.Arg342Ter (c.1024C>T) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 28 submitters; last evaluated 2026-08-03). Absent from gnomAD v4.1; Associated with adrenocortical carcinoma, hereditary.

What condition is associated with TP53 p.Arg342Ter (c.1024C>T)?

TP53 p.Arg342Ter (c.1024C>T) is associated with adrenocortical carcinoma, hereditary, bone osteosarcoma, exocrine pancreatic carcinoma (ClinVar).

How common is TP53 p.Arg342Ter (c.1024C>T) in the general population?

TP53 p.Arg342Ter (c.1024C>T) is absent from gnomAD v4.1 (gnomAD).

How is Adrenocortical carcinoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

TP53 p.Arg342Ter

c.1024C>T · rs730882029 · VCV182970

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 28 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

adrenocortical carcinoma, hereditary

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 10 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -0.12, phastCons 1
Overall
CADD	36.0	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.Arg342Ter
Coding: c.1024C>T
MANE Select: NM_000546
dbSNP: rs730882029
Type: single nucleotide variant
Location: chr17:7670685 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 342: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with carm1' region; an α-helix; the 'interaction with hipk2' region; the 'oligomerization' region; the 'interaction with hipk1' region

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

Disease context

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

Also linked: bone osteosarcoma exocrine pancreatic carcinoma gallbladder cancer colorectal cancer hepatocellular carcinoma choroid plexus papilloma basal cell carcinoma, susceptibility to, 7 hereditary neoplastic syndrome nasopharyngeal carcinoma hereditary breast carcinoma Li-Fraumeni syndrome ovarian neoplasm glioma susceptibility 1 bone marrow failure syndrome 5

For Adrenocortical carcinoma (Orphanet):

Inheritance: Not applicable
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TP53 p.Arg342Pro Pathogenic ★★★ same residue
TP53 p.Arg342Gln Likely benign ★★★ same residue
TP53 p.Arg342Gly Uncertain significance ★★ same residue
TP53 p.Arg342= Benign/Likely benign ★★ same residue
TP53 p.Arg342Leu Uncertain significance ★ ⚠ same residue
TP53 p.Arg342fs Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg342_Glu343insTer Pathogenic 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-arg342ter (accessed [today's date]).

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