PALB2 p.Pro135=
c.405T>C · rs786201586 · VCV184637
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00502%, amr)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.52 | GERP 0.73, phastCons 0.001 |
| Overall | ||
| CADD | 7.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00502%
Admixed American · 3/59,808 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000669%
Overall
0.000682%
11/1,612,970 alleles · very rare
exomes 10/1,461,342 · genomes 1/151,628 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00502% | 19,936 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,448 |
| European (non-Finnish) | 0.000593% | 168,529 |
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
- PALB2
- Protein
- p.Pro135=
- Coding
- c.405T>C
- MANE Select
- NM_024675
- dbSNP
- rs786201586
- Type
- single nucleotide variant
- Location
- chr16:23636141 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.07 · 4 PDB
- Residue 135
- the 'interaction with rad51' region; the 'required for its oligomerization and is important for its focal concentration at dna damage sites' region; the 'disordered' region; the 'dna-binding (with the preference d loop > dsdna > ssdna)' region; the 'interaction with brca1' region
Similar variants
- PALB2 p.Pro135Arg Uncertain significance ★★ ⚠ same residue
- PALB2 p.Pro135Leu Uncertain significance ★★ ⚠ same residue
- PALB2 p.Pro135_Ser136insTer Pathogenic ★★ same residue
- PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
- PALB2 p.Arg1117Lys Pathogenic ★★★ ⚠ same condition
- PALB2 p.Gln228Ter Pathogenic ★★★ same condition
- PALB2 p.Gln692Ter Likely pathogenic ★★★ same condition
- PALB2 p.Glu3Ter 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-pro135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown