Is PALB2 p.Arg26fs (c.72del) pathogenic?

PALB2 p.Arg26fs (c.72del) is classified Pathogenic/Likely pathogenic in PALB2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-26). Very rare (popmax 8.47e-05%, nfe); Associated with pancreatic cancer, susceptibility to, 3.

What condition is associated with PALB2 p.Arg26fs (c.72del)?

PALB2 p.Arg26fs (c.72del) is associated with pancreatic cancer, susceptibility to, 3, Fanconi anemia complementation group N, hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Arg26fs (c.72del) in the general population?

PALB2 p.Arg26fs (c.72del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PALB2 p.Arg26fs

c.72del · rs180177142 · VCV126766

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

pancreatic cancer, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,944 alleles

Overall 6.84e-05% 1/1,461,784 alleles · very rare

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.Arg26fs
Coding: c.72del
MANE Select: NM_024675
dbSNP: rs180177142
Type: Deletion
Location: chr16:23638106 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 26: the 'interaction with rad51' region; the 'required for its oligomerization and is important for its focal concentration at dna damage sites' region; an α-helix; 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

pancreatic cancer, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group N hereditary neoplastic syndrome hereditary breast carcinoma breast-ovarian cancer, familial, susceptibility to, 5

Similar variants

PALB2 p.Arg26= Benign/Likely benign ★★ same residue
PALB2 p.Arg26Met Uncertain significance ★ ⚠ same residue
PALB2 p.Arg26Ser Uncertain significance ★ ⚠ same residue
PALB2 p.Arg26Thr Uncertain significance ★ ⚠ same residue
PALB2 p.Glu178fs Pathogenic ★★★ same condition
PALB2 p.Gly1121fs Likely pathogenic ★★★ same condition
PALB2 p.Leu531fs Pathogenic ★★★ same condition
PALB2 p.Ser172fs 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-arg26fs (accessed [today's date]).

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