Is TP53 p.Asp393= (c.1179C>T) pathogenic?

TP53 p.Asp393= (c.1179C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-07). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Asp393= (c.1179C>T)?

TP53 p.Asp393= (c.1179C>T) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Asp393= (c.1179C>T) in the general population?

TP53 p.Asp393= (c.1179C>T) is absent from gnomAD v4.1 (gnomAD).

How is Li-Fraumeni syndrome inherited?

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

TP53 p.Asp393=

c.1179C>T · rs2072829931 · VCV1559869

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -2.1, phastCons 1
Overall
CADD	6.838	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.Asp393=
Coding: c.1179C>T
MANE Select: NM_000546
dbSNP: rs2072829931
Type: single nucleotide variant
Location: chr17:7669612 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 393: the 'interaction with carm1' region; the 'disordered' region; the 'interaction with morn3' region

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.Asp393Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asp393Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asp393Gly Uncertain significance ★ ⚠ same residue
TP53 p.Asp393His Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asp393Val Uncertain significance ★ ⚠ same residue
TP53 p.Asp393delinsProTrpGlyAspSerGlnValSerThrThrProThrGlnSerCysSerAlaThrGlnThrAlaHisSerAlaAsnAlaGlySerGlyThrLeuGluAlaXaaXaaXaaXaaLysLysLysArgArgAlaTer Uncertain significance ★ same residue
TP53 p.Asp393Tyr Likely benign ★ ⚠ 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-asp393 (accessed [today's date]).

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