Is TP53 p.Glu349= (c.1047A>G) pathogenic?

TP53 p.Glu349= (c.1047A>G) is classified Benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Glu349= (c.1047A>G)?

TP53 p.Glu349= (c.1047A>G) is associated with Li-Fraumeni syndrome 1 (ClinVar).

How common is TP53 p.Glu349= (c.1047A>G) in the general population?

TP53 p.Glu349= (c.1047A>G) is absent from gnomAD v4.1 (gnomAD).

TP53 p.Glu349=

c.1047A>G · VCV4071082

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.025	GERP -3.5, phastCons 0.057
Overall
CADD	8.576	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.Glu349=
Coding: c.1047A>G
MANE Select: NM_000546
Type: single nucleotide variant
Location: chr17:7670662 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 349: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with carm1' region; an α-helix; 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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Glu349Ter Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Glu349Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Glu349Lys Uncertain significance ★ ⚠ same residue
TP53 p.Glu349Gly Likely 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-glu349 (accessed [today's date]).

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