PALB2 p.Pro225fs
c.672_673del · VCV4533160
Likely pathogenic
Single submitter
Classification
Likely 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 in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP -2.4, phastCons 0.51 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PALB2
- Protein
- p.Pro225fs
- Coding
- c.672_673del
- MANE Select
- NM_024675
- Type
- Deletion
- Location
- chr16:23635873 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.07 · 4 PDB
- Residue 225
- the 'dna-binding (with the preference d loop > dsdna > ssdna)' region; the 'interaction with brca1' region
Similar variants
- PALB2 p.Pro225Ser Uncertain significance ★★ ⚠ same residue
- PALB2 p.Pro225= Benign/Likely benign ★★ same residue
- PALB2 p.Pro225Arg Uncertain significance ★ ⚠ same residue
- PALB2 p.Glu178fs Pathogenic ★★★ same type
- PALB2 p.Gly1121fs Likely pathogenic ★★★ same type
- PALB2 p.Leu531fs Pathogenic ★★★ same type
- PALB2 p.Ser172fs Pathogenic ★★★ same type
- PALB2 p.Leu1171fs 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/palb2-p-pro225fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown