Is TP53 p.Cys277= (c.831T>C) pathogenic?

TP53 p.Cys277= (c.831T>C) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-04-04). Very rare (popmax 8.47e-05%, nfe); Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Cys277= (c.831T>C)?

TP53 p.Cys277= (c.831T>C) is associated with Li-Fraumeni syndrome 1, hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Cys277= (c.831T>C) in the general population?

TP53 p.Cys277= (c.831T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TP53 p.Cys277=

c.831T>C · rs1057523347 · VCV389164

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 3.1	GERP -1.8, phastCons 1
Overall
CADD	11.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.2e-05% 1/1,614,054 alleles · very rare exomes 1/1,461,868 · genomes 0/152,186 · 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.Cys277=
Coding: c.831T>C
MANE Select: NM_000546
dbSNP: rs1057523347
Type: single nucleotide variant
Location: chr17:7673789 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 277: a DNA-binding region; the 'interaction with axin1' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in an osteosarcoma with no family history; germline mutation and in sporadic cancers; somatic mutation); the 'interaction with e4f1' region; the 'interaction with dna' region; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region

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.Cys277Gly Likely pathogenic ★★★ same residue
TP53 p.Cys277Arg Uncertain significance ★★★ ⚠ same residue
TP53 p.Cys277Ter Pathogenic ★★ same residue
TP53 p.Cys277Ser Uncertain significance ★★ ⚠ same residue
TP53 p.Cys277Trp Uncertain significance ★★ ⚠ same residue
TP53 p.Cys277Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Cys277Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Cys277fs Pathogenic ★ 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-cys277 (accessed [today's date]).

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