Is MDM2 p.Pro320= (c.960C>G) pathogenic?

MDM2 p.Pro320= (c.960C>G) is classified Likely benign in MDM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). Ultra-rare (popmax 0.0822%, mid); Associated with Accelerated tumor formation, susceptibility to.

What condition is associated with MDM2 p.Pro320= (c.960C>G)?

MDM2 p.Pro320= (c.960C>G) is associated with Accelerated tumor formation, susceptibility to (ClinVar).

How common is MDM2 p.Pro320= (c.960C>G) in the general population?

MDM2 p.Pro320= (c.960C>G) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

MDM2 p.Pro320=

c.960C>G · rs373214952 · VCV1124507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Conditions

Accelerated tumor formation, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -2.6	GERP -3.7
Overall
CADD	0.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0285%

Overall 0.00558% 90/1,613,730 alleles · ultra-rare exomes 84/1,461,670 · genomes 6/152,060 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
South Asian	0.0429%	2,334
Remaining individualsnot grpmax-eligible	0.0048%	20,825
Admixed American	0.00334%	29,975
European (non-Finnish)	0.00322%	31,051
African / African-American	0.00267%	37,439
East Asian	0.00223%	44,860

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: MDM2
Protein: p.Pro320=
Coding: c.960C>G
MANE Select: NM_002392
dbSNP: rs373214952
Type: single nucleotide variant
Location: chr12:68839315 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 320: the 'region ii' region; the 'necessary for interaction with usp2' region; a turn

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 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
MDM2 p.Glu273Ala Uncertain significance ★★ ⚠ same condition
MDM2 p.Gly341Glu Uncertain significance ★★ ⚠ same condition
MDM2 p.Ser122Leu 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-pro320 (accessed [today's date]).

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