Is PALB2 p.Ser270= (c.810C>T) pathogenic?

PALB2 p.Ser270= (c.810C>T) is classified Benign in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Ser270= (c.810C>T)?

PALB2 p.Ser270= (c.810C>T) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Ser270= (c.810C>T) in the general population?

PALB2 p.Ser270= (c.810C>T) 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.Ser270=

c.810C>T · VCV3903880

Benign Single submitter

Classification

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 3.1	GERP -1.9, phastCons 0.37
Overall
CADD	3.59	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.Ser270=
Coding: c.810C>T
MANE Select: NM_024675
Type: single nucleotide variant
Location: chr16:23635736 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 270: the 'disordered' region; the 'dna-binding (with the preference d loop > dsdna > ssdna)' region; the 'interaction with brca1' 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.Ser270Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser270Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Ser270Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Ser270_Thr274del Uncertain significance ★ same residue
PALB2 p.Ser270Cys Uncertain significance ★ ⚠ same residue
PALB2 p.Ser270Ile Uncertain significance ⚠ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys 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-ser270 (accessed [today's date]).

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