PPM1D p.Leu538=
c.1614A>G · rs768449890 · VCV2713205
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
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 0.66 | GERP -1.9, phastCons 0.95 |
| Overall | ||
| CADD | 5.428 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,180,040 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00285%
46/1,614,110 alleles · very rare
exomes 43/1,461,866 · genomes 3/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,443 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| African / African-American | 0.00133% | 74,946 |
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
- PPM1D
- Protein
- p.Leu538=
- Coding
- c.1614A>G
- MANE Select
- NM_003620
- dbSNP
- rs768449890
- Type
- single nucleotide variant
- Location
- chr17:60663348 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.15 · 1 PDB
- Residue 538
- a UniProt-annotated variant site (in jdvs); a UniProt-annotated variant site (in oc; may be associated with disease susceptibility); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility; gain-of-function mutation that results in increased negative regulation of p53 expression in response to ionizing radiation exposure); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility); the 'disordered' region
Similar variants
- PPM1D p.Leu538_Glu539insTer Uncertain significance ★ same residue
- PPM1D p.Cys407Ter Pathogenic/Likely pathogenic ★★ same type
- PPM1D p.Gln404Ter Pathogenic ★★ same type
- PPM1D p.Gln462Ter Likely pathogenic ★★ same type
- PPM1D p.Glu423Ter Pathogenic ★★ same type
- PPM1D p.Ser421Ter Pathogenic/Likely pathogenic ★★ same type
- PPM1D p.Trp427Ter Pathogenic ★★ same type
- PPM1D p.Arg357Cys 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/ppm1d-p-leu538 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown