Is TP53 p.Ser241Phe (c.722C>T) pathogenic?

TP53 p.Ser241Phe (c.722C>T) is classified Pathogenic/Likely pathogenic in TP53 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.999); Very rare (popmax 8.48e-05%, nfe); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Ser241Phe (c.722C>T)?

TP53 p.Ser241Phe (c.722C>T) is associated with Li-Fraumeni syndrome, bone osteosarcoma, exocrine pancreatic carcinoma (ClinVar).

How common is TP53 p.Ser241Phe (c.722C>T) in the general population?

TP53 p.Ser241Phe (c.722C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Li-Fraumeni syndrome inherited?

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

What do computational predictors say about TP53 p.Ser241Phe (c.722C>T)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

TP53 p.Ser241Phe

c.722C>T · rs28934573 · VCV12359

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic ✓ concordant with ClinVar · top 3% in TP53
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -13.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.16, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,940 alleles

Overall 6.2e-05% 1/1,613,804 alleles · very rare exomes 1/1,461,780 · genomes 0/152,024 · joint denominator

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.Ser241Phe
Coding: c.722C>T
MANE Select: NM_000546
dbSNP: rs28934573
Type: single nucleotide variant
Location: chr17:7674241 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 241: 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; 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 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

Also linked: bone osteosarcoma exocrine pancreatic carcinoma colorectal cancer hepatocellular carcinoma adrenocortical carcinoma, hereditary choroid plexus papilloma basal cell carcinoma, susceptibility to, 7 hereditary neoplastic syndrome nasopharyngeal carcinoma hereditary breast carcinoma hepatoblastoma ovarian neoplasm lip and oral cavity carcinoma glioma susceptibility 1 bone marrow failure syndrome 5

For Li-Fraumeni syndrome (Orphanet):

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

Similar variants

TP53 p.Ser241Ala Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Cys Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Thr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Tyr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241= Benign/Likely benign ★★ same residue
TP53 p.Ser241Pro Uncertain significance ★ ⚠ same residue
TP53 p.Ser241fs 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-ser241phe (accessed [today's date]).

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