Is PALB2 p.Pro388del (c.1160CTC[1]) pathogenic?

PALB2 p.Pro388del (c.1160CTC[1]) is classified Uncertain significance in PALB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-18). Very rare (popmax 0.00167%, amr); Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Pro388del (c.1160CTC[1])?

PALB2 p.Pro388del (c.1160CTC[1]) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Pro388del (c.1160CTC[1]) in the general population?

PALB2 p.Pro388del (c.1160CTC[1]) is very rare (popmax 0.00167%, amr) (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.Pro388del

c.1160CTC[1] · rs1306677139 · VCV1443457

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.9, phastCons 0.71

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Overall 6.84e-05% 1/1,461,708 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.Pro388del
Coding: c.1160CTC[1]
MANE Select: NM_024675
dbSNP: rs1306677139
Type: Microsatellite
Location: chr16:23635381 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 388: a UniProt-annotated variant site (risk factor for brovca5); the 'dna-binding (with the preference d loop > dsdna > ssdna)' 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.Pro388dup Uncertain significance ★ same residue
PALB2 p.Pro388fs Pathogenic ★★ same residue
PALB2 p.Pro388Ser Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro388= Benign/Likely benign ★★ same residue
PALB2 p.Pro388Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Asn930fs Pathogenic ★★★ same condition
PALB2 p.Arg975fs Pathogenic ★★ same condition
PALB2 p.Asp161fs 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-pro388del (accessed [today's date]).

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