PPM1D p.Ser412fs
c.1233_1234del · VCV3336919
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 27 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 2.3, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PPM1D
- Protein
- p.Ser412fs
- Coding
- c.1233_1234del
- MANE Select
- NM_003620
- Type
- Deletion
- Location
- chr17:60656814 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.15 · 1 PDB
- Residue 412
- a UniProt-annotated variant site (in jdvs)
Similar variants
- PPM1D p.Arg536fs Likely pathogenic ★★ same type
- PPM1D p.Pro413fs Likely pathogenic ★★ same type
- PPM1D p.Tyr401fs Pathogenic/Likely pathogenic ★★ same type
- PPM1D p.Arg429_Val430insTer Pathogenic ★ same type
- PPM1D p.Asn431_Ser432insTer Likely pathogenic ★ same type
- PPM1D p.Cys407fs Likely pathogenic ★ same type
- PPM1D p.Cys478fs Likely pathogenic ★ same type
- PPM1D p.Glu405fs Likely pathogenic ★ 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-ser412fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown