Is PALB2 p.Glu19= (c.57G>A) pathogenic?

PALB2 p.Glu19= (c.57G>A) is classified Benign in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). No allele count reported in gnomAD v4.1 (AN 1,613,724); Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Glu19= (c.57G>A)?

PALB2 p.Glu19= (c.57G>A) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Glu19= (c.57G>A) in the general population?

PALB2 p.Glu19= (c.57G>A) is no allele count reported in gnomAD v4.1 (AN 1,613,724) (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.Glu19=

c.57G>A · VCV3903978

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,724)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3, phastCons 1
Overall
CADD	7.771	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,724). 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.Glu19=
Coding: c.57G>A
MANE Select: NM_024675
Type: single nucleotide variant
Location: chr16:23638121 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 19: 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

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.Glu19Asp Uncertain significance ★★ ⚠ same residue
PALB2 p.Glu19Ter Pathogenic ★ same residue
PALB2 p.Glu19delinsAspPhePhePhePhePhePheXaaXaaXaaXaaArgAspGlyValSerProCysTer Pathogenic ★ same residue
PALB2 p.Glu19Gly Uncertain significance ★ ⚠ same residue
PALB2 p.Glu19Lys Uncertain significance ★ ⚠ 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-glu19 (accessed [today's date]).

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