Is PALB2 p.Val504= (c.1512T>C) pathogenic?

PALB2 p.Val504= (c.1512T>C) is classified Likely benign in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-20). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Val504= (c.1512T>C)?

PALB2 p.Val504= (c.1512T>C) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Val504= (c.1512T>C) in the general population?

PALB2 p.Val504= (c.1512T>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

PALB2 p.Val504=

c.1512T>C · rs2142413814 · VCV2733526

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast carcinoma

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 1.7	GERP -2.3
Overall
CADD	3.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PALB2
Protein: p.Val504=
Coding: c.1512T>C
MANE Select: NM_024675
dbSNP: rs2142413814
Type: single nucleotide variant
Location: chr16:23635034 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 504: 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

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

PALB2 p.Val504Phe Uncertain significance ★★ ⚠ same residue
PALB2 p.Val504Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Val504Leu 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-val504 (accessed [today's date]).

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