Is MDM2 p.Leu203= (c.607C>T) pathogenic?

MDM2 p.Leu203= (c.607C>T) is classified Benign in MDM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.89%, afr); Associated with Accelerated tumor formation, susceptibility to.

What condition is associated with MDM2 p.Leu203= (c.607C>T)?

MDM2 p.Leu203= (c.607C>T) is associated with Accelerated tumor formation, susceptibility to (ClinVar).

How common is MDM2 p.Leu203= (c.607C>T) in the general population?

MDM2 p.Leu203= (c.607C>T) is low-frequency (popmax 2.89%, afr) (gnomAD).

MDM2 p.Leu203=

c.607C>T · rs1795480 · VCV472749

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.89%, afr)

Conditions

Accelerated tumor formation, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.5, phastCons 1
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.89% African / African-American · 2,166/74,972 alleles

Filtering AF 2.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.75%

Overall 1.52% 24,451/1,613,910 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.89%	35
Finnishnot grpmax-eligible	2.17%	46
European (non-Finnish)	1.6%	62
Remaining individualsnot grpmax-eligible	1.47%	68
Middle Eastern	1.22%	82
Admixed American	0.801%	125
Ashkenazi Jewishnot grpmax-eligible	0.517%	193
South Asian	0.412%	243
East Asian	0.00223%	44,864

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.Leu203=
Coding: c.607C>T
MANE Select: NM_002392
dbSNP: rs1795480
Type: single nucleotide variant
Location: chr12:68828854 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 148 PDB
Residue 203: the 'interaction with pyhin1 and necessary for interaction with rffl and rnf34' region; the 'interaction with mtbp' region; the 'mediates interaction with rad54b' 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-leu203 (accessed [today's date]).

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