Is TP53 p.Cys242= (c.726C>T) pathogenic?

TP53 p.Cys242= (c.726C>T) is classified Likely benign in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Cys242= (c.726C>T)?

TP53 p.Cys242= (c.726C>T) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Cys242= (c.726C>T) in the general population?

TP53 p.Cys242= (c.726C>T) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Cys242=

c.726C>T · rs375874539 · VCV2169587

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,818)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.9, phastCons 1
Overall
CADD	11.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,818). 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.Cys242=
Coding: c.726C>T
MANE Select: NM_000546
dbSNP: rs375874539
Type: single nucleotide variant
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

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

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Cys242Tyr Pathogenic/Likely pathogenic ★★ 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.Cys242Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Cys242Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Cys242fs Pathogenic ★★ same residue
TP53 p.Cys242_Met243insThrCys Uncertain significance ★ 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-cys242 (accessed [today's date]).

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