Is PALB2 p.Pro117= (c.351T>C) pathogenic?

PALB2 p.Pro117= (c.351T>C) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0385%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Pro117= (c.351T>C)?

PALB2 p.Pro117= (c.351T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Pro117= (c.351T>C) in the general population?

PALB2 p.Pro117= (c.351T>C) is ultra-rare (popmax 0.0385%, amr) (gnomAD).

PALB2 p.Pro117=

c.351T>C · rs763330757 · VCV215937

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, amr)

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 1.1	GERP -3
Overall
CADD	4.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0385% Admixed American · 23/59,802 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.00161% 26/1,613,184 alleles · ultra-rare exomes 24/1,461,234 · genomes 2/151,950 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0385%	2,600
European (non-Finnish)	0.000254%	393,294

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.Pro117=
Coding: c.351T>C
MANE Select: NM_024675
dbSNP: rs763330757
Type: single nucleotide variant
Location: chr16:23636195 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 117: 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

PALB2 p.Pro117Leu Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro117Ala Uncertain significance ★ ⚠ same residue
PALB2 p.Pro117Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro117Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys Pathogenic ★★★ ⚠ same condition
PALB2 p.Gln228Ter Pathogenic ★★★ same condition
PALB2 p.Gln692Ter Likely 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-pro117 (accessed [today's date]).

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