PALB2 p.Val398=
c.1194G>A · rs61755173 · VCV126592
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 31 submitters
gnomAD v4.1
Rare
rare (popmax 0.186%, nfe)
Conditions
5
breast-ovarian cancer, familial, susceptibility to, 5
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 0.41 | GERP -3.5, phastCons 0.96 |
| Overall | ||
| CADD | 6.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.186%
European (non-Finnish) · 2,192/1,180,032 alleles
Filtering AF
0.179%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.177%
Overall
0.147%
2,377/1,613,992 alleles · rare
exomes 2,227/1,461,664 · genomes 150/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.186% | 538 |
| Remaining individualsnot grpmax-eligible | 0.138% | 727 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0946% | 1,057 |
| Admixed American | 0.0533% | 1,876 |
| African / African-American | 0.04% | 2,502 |
| Finnishnot grpmax-eligible | 0.0125% | 7,978 |
| South Asian | 0.0011% | 91,088 |
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.Val398=
- Coding
- c.1194G>A
- MANE Select
- NM_024675
- dbSNP
- rs61755173
- Type
- single nucleotide variant
- Location
- chr16:23635352 (GRCh38)
- Gene constraint
- LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.07 · 4 PDB
- Residue 398
- the 'cham (chromatin-association motif); required for chromatin association, mediates nucleosome association' region; a UniProt-annotated variant site (risk factor for brovca5); the 'dna-binding (with the preference d loop > dsdna > ssdna)' region
Similar variants
- PALB2 p.Val398Gly Uncertain significance ★★ ⚠ same residue
- PALB2 p.Val398Leu Uncertain significance ★★ ⚠ same residue
- PALB2 p.Val398Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- PALB2 p.Val398fs 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
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-val398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown