Is TP53 p.Ser241= (c.723C>T) pathogenic?

TP53 p.Ser241= (c.723C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-03). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Ser241= (c.723C>T)?

TP53 p.Ser241= (c.723C>T) is associated with Li-Fraumeni syndrome 1, hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Ser241= (c.723C>T) in the general population?

TP53 p.Ser241= (c.723C>T) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Ser241=

c.723C>T · rs2543562410 · VCV1757851

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Li-Fraumeni syndrome 1

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 1.8	GERP -4.5, phastCons 1
Overall
CADD	9.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53
Protein: p.Ser241=
Coding: c.723C>T
MANE Select: NM_000546
dbSNP: rs2543562410
Type: single nucleotide variant
Location: chr17:7674240 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome Li-Fraumeni syndrome

Similar variants

TP53 p.Ser241Ala Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Cys Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Phe Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Thr Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Ser241Tyr Pathogenic/Likely pathogenic ★★ 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-ser241 (accessed [today's date]).

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