Is PALB2 p.Pro473= (c.1419A>C) pathogenic?

PALB2 p.Pro473= (c.1419A>C) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 23 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.09%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 5.

What condition is associated with PALB2 p.Pro473= (c.1419A>C)?

PALB2 p.Pro473= (c.1419A>C) is associated with breast-ovarian cancer, familial, susceptibility to, 5, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is PALB2 p.Pro473= (c.1419A>C) in the general population?

PALB2 p.Pro473= (c.1419A>C) is low-frequency (popmax 1.09%, afr) (gnomAD).

PALB2 p.Pro473=

c.1419A>C · rs62625275 · VCV126601

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 23 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, afr)

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 -0.14	GERP -0.67
Overall
CADD	2.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% African / African-American · 821/75,062 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.0592% 956/1,614,242 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	91
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0733%	1,364
South Asian	0.00439%	22,772
European (non-Finnish)	0.00195%	51,306

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.Pro473=
Coding: c.1419A>C
MANE Select: NM_024675
dbSNP: rs62625275
Type: single nucleotide variant
Location: chr16:23635127 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 473: 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: hereditary breast ovarian cancer syndrome breast cancer hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

PALB2 p.Pro473Ala Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro473Ser Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro473Arg Uncertain significance ★ ⚠ same residue
PALB2 p.Pro473Leu Uncertain significance ★ ⚠ same residue
PALB2 p.Pro473fs Pathogenic ★ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys Pathogenic ★★★ ⚠ same condition
PALB2 p.Gln228Ter 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-pro473 (accessed [today's date]).

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