Is PALB2 p.Pro719= (c.2157T>C) pathogenic?

PALB2 p.Pro719= (c.2157T>C) is classified Likely benign in PALB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-18). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Pro719= (c.2157T>C)?

PALB2 p.Pro719= (c.2157T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Pro719= (c.2157T>C) in the general population?

PALB2 p.Pro719= (c.2157T>C) is absent from gnomAD v4.1 (gnomAD).

PALB2 p.Pro719=

c.2157T>C · rs2142379569 · VCV1786835

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 -1.9
Overall
CADD	0.656	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PALB2
Protein: p.Pro719=
Coding: c.2157T>C
MANE Select: NM_024675
dbSNP: rs2142379569
Type: single nucleotide variant
Location: chr16:23629997 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 719: a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5)

Full PALB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

PALB2 p.Pro719Ser Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro719Ala Uncertain significance ★ ⚠ same residue
PALB2 p.Pro719Arg Uncertain significance ★ ⚠ same residue
PALB2 p.Pro719Thr Uncertain significance ★ ⚠ same residue
PALB2 p.Pro719fs Pathogenic ★ 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-pro719 (accessed [today's date]).

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