Is PALB2 p.Ser869= (c.2607C>T) pathogenic?

PALB2 p.Ser869= (c.2607C>T) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 22 submitters; last evaluated 2026-02-04). Rare (popmax 0.592%, afr); Associated with Breast and/or ovarian cancer.

What condition is associated with PALB2 p.Ser869= (c.2607C>T)?

PALB2 p.Ser869= (c.2607C>T) is associated with Breast and/or ovarian cancer, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Ser869= (c.2607C>T) in the general population?

PALB2 p.Ser869= (c.2607C>T) is rare (popmax 0.592%, afr) (gnomAD).

PALB2 p.Ser869=

c.2607C>T · rs45542234 · VCV136135

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 22 submitters

gnomAD v4.1

Rare

rare (popmax 0.592%, afr)

Conditions

Breast and/or ovarian cancer

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 -7.8	GERP -3.7
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.592% African / African-American · 444/74,990 alleles

Filtering AF 0.547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.529%

Overall 0.0332% 536/1,614,064 alleles · rare exomes 268/1,461,884 · genomes 268/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.592%	169
Admixed American	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.032%	3,125
South Asian	0.0242%	4,140
Middle Eastern	0.0165%	6,060
East Asian	0.00446%	22,436
European (non-Finnish)	0.00161%	62,107

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.Ser869=
Coding: c.2607C>T
MANE Select: NM_024675
dbSNP: rs45542234
Type: single nucleotide variant
Location: chr16:23626377 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 869: the 'required for interaction with polh and polh dna synthesis stimulation' region; the 'interaction with rad51, brca2 and polh' region; a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5); a β-strand

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

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

PALB2 p.Ser869Cys Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser869Phe Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser869Tyr Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser869Pro Uncertain significance ★ ⚠ same residue
PALB2 p.Ser869_Val870insTer Pathogenic/Likely 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-ser869 (accessed [today's date]).

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