Is PALB2 p.Ser524= (c.1572A>G) pathogenic?

PALB2 p.Ser524= (c.1572A>G) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 30 submitters; last evaluated 2026-06-01). Rare (popmax 0.562%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 5.

What condition is associated with PALB2 p.Ser524= (c.1572A>G)?

PALB2 p.Ser524= (c.1572A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 5, breast cancer, Fanconi anemia complementation group N (ClinVar).

How common is PALB2 p.Ser524= (c.1572A>G) in the general population?

PALB2 p.Ser524= (c.1572A>G) is rare (popmax 0.562%, nfe) (gnomAD).

PALB2 p.Ser524=

c.1572A>G · rs45472400 · VCV126608

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 30 submitters

gnomAD v4.1

Rare

rare (popmax 0.562%, nfe)

Conditions

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 -1.4	GERP -3.5
Overall
CADD	1.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.562% European (non-Finnish) · 6,632/1,180,046 alleles

Filtering AF 0.551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.546%

Overall 0.466% 7,529/1,614,194 alleles · rare exomes 7,061/1,461,892 · genomes 468/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.562%	178
Remaining individualsnot grpmax-eligible	0.421%	238
South Asian	0.333%	301
Admixed American	0.268%	373
Finnishnot grpmax-eligible	0.153%	653
Middle Eastern	0.115%	866
African / African-American	0.076%	1,317
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701

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.Ser524=
Coding: c.1572A>G
MANE Select: NM_024675
dbSNP: rs45472400
Type: single nucleotide variant
Location: chr16:23634974 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 524: the 'disordered' region; a UniProt-annotated variant site (risk factor for brovca5); the 'dna-binding (with the preference d loop > dsdna > ssdna)' region

Full PALB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast cancer Fanconi anemia complementation group N hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

PALB2 p.Ser524Ter Pathogenic ★★ same residue
PALB2 p.Ser524Leu Likely benign ★ same residue
PALB2 p.Ser524Arg Uncertain significance ★★ 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-ser524 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown