Is TP53 p.Thr329= (c.987C>T) pathogenic?

TP53 p.Thr329= (c.987C>T) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-04). Very rare (popmax 8.48e-05%, nfe); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Thr329= (c.987C>T)?

TP53 p.Thr329= (c.987C>T) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Thr329= (c.987C>T) in the general population?

TP53 p.Thr329= (c.987C>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.

TP53 p.Thr329=

c.987C>T · rs2151010987 · VCV1995393

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

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

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.259	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -2.6, phastCons 1
Overall
CADD	7.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,936 alleles

Overall 6.2e-05% 1/1,614,004 alleles · very rare exomes 1/1,461,766 · genomes 0/152,238 · 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.Thr329=
Coding: c.987C>T
MANE Select: NM_000546
dbSNP: rs2151010987
Type: single nucleotide variant
Location: chr17:7673541 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 329: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with carm1' region; a β-strand; the 'interaction with hipk2' region; the 'oligomerization' region; the 'interaction with hipk1' 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.Thr329Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Thr329Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Thr329fs Pathogenic ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>A Pathogenic ★★★ same condition
TP53 p.Ala138Pro Likely pathogenic ★★★ same condition
TP53 p.Ala138Val 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-thr329 (accessed [today's date]).

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