Is PALB2 p.Pro1111fs (c.3332del) pathogenic?

PALB2 p.Pro1111fs (c.3332del) is classified Pathogenic in PALB2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-07). No gnomAD frequency available for this variant; Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Pro1111fs (c.3332del)?

PALB2 p.Pro1111fs (c.3332del) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Pro1111fs (c.3332del) in the general population?

PALB2 p.Pro1111fs (c.3332del) is no gnomAD frequency available for this variant (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.Pro1111fs

c.3332del · rs1597066595 · VCV803231

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 18 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.73	GERP -3.7

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PALB2
Protein: p.Pro1111fs
Coding: c.3332del
MANE Select: NM_024675
dbSNP: rs1597066595
Type: Deletion
Location: chr16:23607882 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 1111: 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 UniProt-annotated variant site (risk factor for brovca5; risk factor for pnca3)

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

PALB2 p.Pro1111Leu Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro1111= Benign/Likely benign ★★ same residue
PALB2 p.Pro1111Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro1111Ser 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-pro1111fs (accessed [today's date]).

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