Is TP53 p.Cys242Ser (c.725_726delinsCA) pathogenic?

TP53 p.Cys242Ser (c.725726delinsCA) is classified Uncertain significance in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). No gnomAD frequency available for this variant; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Cys242Ser (c.725_726delinsCA)?

TP53 p.Cys242Ser (c.725_726delinsCA) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Cys242Ser (c.725_726delinsCA) in the general population?

TP53 p.Cys242Ser (c.725_726delinsCA) is no gnomAD frequency available for this variant (gnomAD).

How is Li-Fraumeni syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TP53 p.Cys242Ser

c.725_726delinsCA · rs2543562123 · VCV2124706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Li-Fraumeni 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 3	GERP -1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Cys242Ser
Coding: c.725_726delinsCA
MANE Select: NM_000546
dbSNP: rs2543562123
Type: Indel
Location: chr17:7674237 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 242: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with the 53bp2 sh3 domain' region; an α-helix; the 'interaction with ccar2' region; a binding site; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation)

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

Disease context

Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Li-Fraumeni syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

TP53 p.Cys242fs Pathogenic ★★ same residue
TP53 p.Cys242Tyr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Cys242= Likely benign ★★ same residue
TP53 p.Cys242Ter Pathogenic ★ same residue
TP53 p.Cys242Trp Pathogenic ★ same residue
TP53 p.Cys242Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Cys242dup Uncertain significance ★ same residue
TP53 p.Cys242Gly 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-cys242ser (accessed [today's date]).

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