Is MDM2 p.Asp179Gly (c.536A>G) pathogenic?

MDM2 p.Asp179Gly (c.536A>G) is classified Uncertain significance in MDM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0735); Ultra-rare (popmax 0.0706%, afr); Associated with Accelerated tumor formation, susceptibility to.

What condition is associated with MDM2 p.Asp179Gly (c.536A>G)?

MDM2 p.Asp179Gly (c.536A>G) is associated with Accelerated tumor formation, susceptibility to (ClinVar).

How common is MDM2 p.Asp179Gly (c.536A>G) in the general population?

MDM2 p.Asp179Gly (c.536A>G) is ultra-rare (popmax 0.0706%, afr) (gnomAD).

What do computational predictors say about MDM2 p.Asp179Gly (c.536A>G)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

MDM2 p.Asp179Gly

c.536A>G · rs138567205 · VCV1482898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0706%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Accelerated tumor formation, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor loss, 12 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.5	GERP 0.69, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 8.3e-06 · regional, not allelic
Overall
CADD	22.2	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 D173G vs ClinVar D179G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0706% African / African-American · 53/75,020 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00378% 61/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0706%	1,415
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.000254%	393,306

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.Asp179Gly
Coding: c.536A>G
MANE Select: NM_002392
dbSNP: rs138567205
Type: single nucleotide variant
Location: chr12:68828783 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 179: the 'disordered' region; the 'interaction with pyhin1 and necessary for interaction with rffl and rnf34' region; the 'interaction with mtbp' region

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-asp179gly (accessed [today's date]).

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