Is TP53 p.Glu51= (c.153A>G) pathogenic?

TP53 p.Glu51= (c.153A>G) is classified Benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Ultra-rare (popmax 0.0165%, mid); Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Glu51= (c.153A>G)?

TP53 p.Glu51= (c.153A>G) is associated with Li-Fraumeni syndrome 1 (ClinVar).

How common is TP53 p.Glu51= (c.153A>G) in the general population?

TP53 p.Glu51= (c.153A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

TP53 p.Glu51=

c.153A>G · VCV4071020

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -3.5
Overall
CADD	0.307	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Overall 6.84e-05% 1/1,461,880 alleles · ultra-rare

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.Glu51=
Coding: c.153A>G
MANE Select: NM_000546
Type: single nucleotide variant
Location: chr17:7676216 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 51: an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' 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

Similar variants

TP53 p.Glu51Ter Pathogenic ★ same residue
TP53 p.Glu51Gly Uncertain significance ★ ⚠ same residue
TP53 p.Glu51Lys Uncertain significance ★ ⚠ same residue
TP53 p.Glu51Asp Benign ★ same residue
TP53 p.Met237Ile Pathogenic ★★★ ⚠ same condition
TP53 p.Val272Met Pathogenic ★★★ same condition
TP53 p.Arg156His Uncertain significance ★★★ ⚠ same condition
TP53 c.673-5C>G Likely benign ★★★ 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-glu51 (accessed [today's date]).

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