Is MDM2 p.Glu429fs (c.1284_1287del) pathogenic?

MDM2 p.Glu429fs (c.12841287del) is classified Uncertain significance in MDM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). Absent from gnomAD; Associated with Accelerated tumor formation, susceptibility to.

What condition is associated with MDM2 p.Glu429fs (c.1284_1287del)?

MDM2 p.Glu429fs (c.1284_1287del) is associated with Accelerated tumor formation, susceptibility to (ClinVar).

How common is MDM2 p.Glu429fs (c.1284_1287del) in the general population?

MDM2 p.Glu429fs (c.1284_1287del) is absent from gnomAD (gnomAD).

MDM2 p.Glu429fs

c.1284_1287del · rs2499257812 · VCV2920098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Accelerated tumor formation, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -1.6, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MDM2
Protein: p.Glu429fs
Coding: c.1284_1287del
MANE Select: NM_002392
dbSNP: rs2499257812
Type: Deletion
Location: chr12:68839637 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 429: the 'necessary for interaction with usp2' region; a modified residue (phosphoserine; by atm)

Full MDM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Accelerated tumor formation, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MDM2 p.Gly233del Uncertain significance ★ same condition
MDM2 c.685-3del Benign ★ same condition
MDM2 c.840+14del Benign ★ same condition
MDM2 c.523+5A>G Uncertain significance ★★ same condition
MDM2 p.Arg332His Uncertain significance ★★ same condition
MDM2 p.Asn117Ser Uncertain significance ★★ ⚠ same condition
MDM2 p.Asn374Ser Uncertain significance ★★ ⚠ same condition
MDM2 p.Gln414Leu Uncertain significance ★★ ⚠ 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/mdm2-p-glu429fs (accessed [today's date]).

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