PALB2 p.Ser985fs
c.2953dup · VCV4130351
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
hereditary neoplastic syndrome
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 9 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -1.3, phastCons 0.99 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PALB2
- Protein
- p.Ser985fs
- Coding
- c.2953dup
- MANE Select
- NM_024675
- Type
- Duplication
- Location
- chr16:23623011 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.07 · 4 PDB
- Residue 985
- the 'required for interaction with polh and polh dna synthesis stimulation' region; the 'interaction with rad51, brca2 and polh' region; a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5)
Similar variants
- PALB2 p.Ser985= Benign/Likely benign ★★ same residue
- PALB2 p.Ser985Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
- PALB2 p.Ala995fs Pathogenic/Likely pathogenic ★★ same condition
- PALB2 p.Arg153fs Pathogenic ★★ same condition
- PALB2 p.Arg464fs Pathogenic ★★ same condition
- PALB2 p.Asn330Ter Pathogenic ★★ same condition
- PALB2 p.Asn540fs Pathogenic ★★ same condition
- PALB2 p.Asn851fs Pathogenic/Likely pathogenic ★★ same condition
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-ser985fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown