Is MDM2 p.Glu101Gln (c.301G>C) pathogenic?

MDM2 p.Glu101Gln (c.301G>C) is classified Uncertain significance in MDM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: ambiguous (0.5091); Absent from gnomAD v4.1.

How common is MDM2 p.Glu101Gln (c.301G>C) in the general population?

MDM2 p.Glu101Gln (c.301G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MDM2 p.Glu101Gln (c.301G>C)?

AlphaMissense predicts ambiguous (score 0.5091) — an in-silico prediction, not a clinical call.

MDM2 p.Glu101Gln

c.301G>C · VCV3394104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5091 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5091	ambiguous
REVEL	0.135	moderately benign-leaning
SaProt	LLR -9.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 6,789 bp · p 9.7e-12 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E95Q vs ClinVar E101Q) — verify the residue.

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: MDM2
Protein: p.Glu101Gln
Coding: c.301G>C
MANE Select: NM_002392
Type: single nucleotide variant
Location: chr12:68816938 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 101: the swib/mdm2 domain; the 'necessary for interaction with usp2' region; the 'sufficient to promote the mitochondrial pathway of apoptosis' region; an α-helix

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

Similar variants

MDM2 c.523+5A>G Uncertain significance ★★ same type
MDM2 p.Ala289Thr Uncertain significance ★★ ⚠ same type
MDM2 p.Arg332His Uncertain significance ★★ ⚠ same type
MDM2 p.Asn117Ser Uncertain significance ★★ ⚠ same type
MDM2 p.Asn374Ser Uncertain significance ★★ ⚠ same type
MDM2 p.Gln414Leu Uncertain significance ★★ ⚠ same type
MDM2 p.Glu273Ala Uncertain significance ★★ ⚠ same type
MDM2 p.Gly341Glu Uncertain significance ★★ ⚠ same type

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-glu101gln (accessed [today's date]).

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