PPM1D p.Ala82=
c.246C>G · rs568338768 · VCV2039049
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.201%, sas)
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 0.09 | GERP 0.46, phastCons 0.67 |
| Overall | ||
| CADD | 13.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.201%
South Asian · 170/84,394 alleles
Filtering AF
0.177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.167%
Overall
0.0112%
174/1,550,706 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.201% | 496 |
| Remaining individualsnot grpmax-eligible | 0.00666% | 15,009 |
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.Ala82=
- Coding
- c.246C>G
- MANE Select
- NM_003620
- dbSNP
- rs568338768
- Type
- single nucleotide variant
- Location
- chr17:60600660 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.15 · 1 PDB
- Residue 82
- the ppm-type phosphatase domain; the 'interaction with chek1' region; the 'disordered' region
Similar variants
- PPM1D p.Ala82Ser Benign ★ 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-ala82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown