Is MDM2 p.Arg71Gln (c.212G>A) pathogenic?

MDM2 p.Arg71Gln (c.212G>A) is classified Uncertain significance in MDM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0776); Very rare (popmax 0.00224%, eas); Associated with Accelerated tumor formation, susceptibility to.

What condition is associated with MDM2 p.Arg71Gln (c.212G>A)?

MDM2 p.Arg71Gln (c.212G>A) is associated with Accelerated tumor formation, susceptibility to (ClinVar).

How common is MDM2 p.Arg71Gln (c.212G>A) in the general population?

MDM2 p.Arg71Gln (c.212G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about MDM2 p.Arg71Gln (c.212G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

MDM2 p.Arg71Gln

c.212G>A · rs1385829631 · VCV1501438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Accelerated tumor formation, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	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	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R65Q vs ClinVar R71Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,668 alleles

Overall 0.000187% 3/1,608,300 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,150
East Asiangrpmax	0.00224%	44,668

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg71Gln
Coding: c.212G>A
MANE Select: NM_002392
dbSNP: rs1385829631
Type: single nucleotide variant
Location: chr12:68816849 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 71: the swib/mdm2 domain; the 'necessary for interaction with usp2' region; the 'sufficient to promote the mitochondrial pathway of apoptosis' region; a β-strand

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-arg71gln (accessed [today's date]).

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