MDM4 p.Pro32=
c.96G>A · rs778790692 · VCV2639832
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.149%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -4.6, phastCons 0.28 |
| Overall | ||
| CADD | 10.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.149%
Middle Eastern · 9/6,056 alleles
Filtering AF
0.0775%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0579%
Overall
0.0118%
190/1,613,708 alleles · rare
exomes 171/1,461,588 · genomes 19/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.149% | 673 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| African / African-American | 0.016% | 6,249 |
| East Asian | 0.0156% | 6,412 |
| European (non-Finnish) | 0.0121% | 8,250 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,800 |
| Admixed American | 0.00667% | 15,001 |
| South Asian | 0.0022% | 45,530 |
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
- MDM4
- Protein
- p.Pro32=
- Coding
- c.96G>A
- MANE Select
- NM_002393
- dbSNP
- rs778790692
- Type
- single nucleotide variant
- Location
- chr1:204526377 (GRCh38)
- Gene constraint
- LOEUF 0.146 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.78 · 39 PDB
- Residue 32
- the swib/mdm2 domain; an α-helix; the 'mediates interaction with rad54b' region
Similar variants
- MDM4 p.Pro32Leu Likely benign ★ ⚠ same residue
- MDM4 p.Ala179Gly Uncertain significance ★★ ⚠ same type
- MDM4 c.511+5G>A Benign/Likely benign ★★ same type
- MDM4 p.Glu303= Benign ★★ same type
- MDM4 p.Lys468= Benign ★★ same type
- MDM4 p.Val74= Benign/Likely benign ★★ same type
- MDM4 p.Ala398Val Uncertain significance ★ ⚠ same type
- MDM4 p.Ala470Ser 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/mdm4-p-pro32 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown