Is TP53 p.Leu32= (c.96G>C) pathogenic?

TP53 p.Leu32= (c.96G>C) is classified Uncertain significance in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Leu32= (c.96G>C)?

TP53 p.Leu32= (c.96G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Leu32= (c.96G>C) in the general population?

TP53 p.Leu32= (c.96G>C) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Leu32=

c.96G>C · VCV4189252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic 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
Pangolin	Δ0.22	loss · gain 0.06 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.1	GERP 1.1, phastCons 1
Overall
CADD	23.9	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.Leu32=
Coding: c.96G>C
MANE Select: NM_000546
Type: single nucleotide variant
Location: chr17:7676382 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 32: an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'transcription activation (acidic)' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Leu32Val Likely benign ★ same residue
TP53 p.Leu32fs 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
TP53 p.Ala347Asp 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-leu32 (accessed [today's date]).

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