PPM1D p.Ala84=
c.252C>G · VCV3671508
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00138%, afr)
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 4.7 | GERP 0.12, phastCons 1 |
| Overall | ||
| CADD | 14.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00138%
African / African-American · 1/72,508 alleles
Filtering AF
0.000298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000216%
Overall
0.000579%
9/1,555,630 alleles · very rare
exomes 6/1,403,358 · genomes 3/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00138% | 72,508 |
| European (non-Finnish) | 0.000693% | 144,288 |
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.Ala84=
- Coding
- c.252C>G
- MANE Select
- NM_003620
- Type
- single nucleotide variant
- Location
- chr17:60600666 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.15 · 1 PDB
- Residue 84
- the ppm-type phosphatase domain; the 'interaction with chek1' region; the 'disordered' region
Similar variants
- PPM1D p.Ala84Val 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-ala84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown