Is TP53 p.Pro72Ser (c.214_215delinsAG) pathogenic?

TP53 p.Pro72Ser (c.214215delinsAG) is classified Uncertain significance in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro72Ser (c.214_215delinsAG)?

TP53 p.Pro72Ser (c.214_215delinsAG) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

TP53 p.Pro72Ser

c.214_215delinsAG · VCV3328172

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 1.1, phastCons 0.015
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic

Variant & gene context

Gene: TP53
Protein: p.Pro72Ser
Coding: c.214_215delinsAG
MANE Select: NM_000546
Type: Indel
Location: chr17:7676154 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 72: a UniProt-annotated variant site (in sporadic cancers; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in); 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

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

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Pro72Cys Uncertain significance ★★★ same residue
TP53 p.Pro72_Val73delinsArgMet Conflicting classifications of pathogenicity ★ same residue
TP53 p.Pro72Ala Likely benign ★★★ same residue
TP53 p.Pro72Arg Benign ★★★ same residue
TP53 p.Pro72His Benign ★★★ ⚠ same residue
TP53 p.Pro72fs Pathogenic ★ same residue
TP53 p.Pro72Gly Uncertain significance ★ same residue
TP53 p.Pro72Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro72ser (accessed [today's date]).

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