Is PALB2 p.Gln55fs (c.163_164dup) pathogenic?

PALB2 p.Gln55fs (c.163164dup) is classified Likely pathogenic in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-30). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Gln55fs (c.163_164dup)?

PALB2 p.Gln55fs (c.163_164dup) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Gln55fs (c.163_164dup) in the general population?

PALB2 p.Gln55fs (c.163_164dup) is absent from gnomAD (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.Gln55fs

c.163_164dup · rs2506534790 · VCV2677470

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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	predicted	premature termination codon in exon 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.69	GERP -3.3

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.Gln55fs
Coding: c.163_164dup
MANE Select: NM_024675
dbSNP: rs2506534790
Type: Duplication
Location: chr16:23637896 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 55: the 'interaction with rad51' region; the 'required for its oligomerization and is important for its focal concentration at dna damage sites' region; 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.Gln55Glu Uncertain significance ★★ ⚠ same residue
PALB2 p.Gln55Leu Uncertain significance ★ ⚠ same residue
PALB2 p.Gln55= Benign ★ same residue
PALB2 p.Ala995fs Pathogenic/Likely pathogenic ★★ same condition
PALB2 p.Arg153fs Pathogenic ★★ same condition
PALB2 p.Arg464fs Pathogenic ★★ same condition
PALB2 p.Asn280fs Pathogenic ★★ same condition
PALB2 p.Asn330Ter 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-gln55fs (accessed [today's date]).

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