Is TP53 p.Val73fs (c.216dup) pathogenic?

TP53 p.Val73fs (c.216dup) is classified Pathogenic in TP53 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-09-10). Very rare (popmax 0.00017%, nfe); Associated with TP53-related disorder.

What condition is associated with TP53 p.Val73fs (c.216dup)?

TP53 p.Val73fs (c.216dup) is associated with TP53-related disorder, adrenocortical carcinoma, hereditary, plasma cell myeloma (ClinVar).

How common is TP53 p.Val73fs (c.216dup) in the general population?

TP53 p.Val73fs (c.216dup) is very rare (popmax 0.00017%, nfe) (gnomAD).

TP53 p.Val73fs

c.216dup · rs730882018 · VCV182957

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

TP53-related disorder

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 0.16	GERP -2.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,588 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,028 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TP53
Protein: p.Val73fs
Coding: c.216dup
MANE Select: NM_000546
dbSNP: rs730882018
Type: Duplication
Location: chr17:7676152 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 73: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region; the 'interaction with wwox' region

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

Disease context

TP53-related disorder

Also linked: adrenocortical carcinoma, hereditary plasma cell myeloma hereditary neoplastic syndrome Li-Fraumeni syndrome Li-fraumeni-like syndrome

Similar variants

TP53 p.Val73Met Benign ★★★ same residue
TP53 p.Val73Ala Uncertain significance ★ ⚠ same residue
TP53 p.Val73Leu Uncertain significance ★ ⚠ same residue
TP53 p.Val73= Likely benign ★ same residue
TP53 p.Val73Glu Likely benign ★ same residue
TP53 p.Ter394LeuextTer? Likely pathogenic ★★★ same condition
TP53 c.375+1dup Pathogenic/Likely pathogenic ★★ same condition
TP53 c.97-1_102dup Pathogenic/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-val73fs (accessed [today's date]).

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