Is PALB2 p.Pro388= (c.1164T>C) pathogenic?

PALB2 p.Pro388= (c.1164T>C) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-28). Very rare (popmax 0.005%, amr); Associated with pancreatic cancer, susceptibility to, 3.

What condition is associated with PALB2 p.Pro388= (c.1164T>C)?

PALB2 p.Pro388= (c.1164T>C) is associated with pancreatic cancer, susceptibility to, 3, Fanconi anemia complementation group N, hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Pro388= (c.1164T>C) in the general population?

PALB2 p.Pro388= (c.1164T>C) is very rare (popmax 0.005%, amr) (gnomAD).

PALB2 p.Pro388=

c.1164T>C · rs1205215998 · VCV517000

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

pancreatic cancer, susceptibility to, 3

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 3.4	GERP 0.64, phastCons 1
Overall
CADD	4.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,614,064 alleles · very rare exomes 4/1,461,722 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
East Asian	0.00223%	44,884

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.Pro388=
Coding: c.1164T>C
MANE Select: NM_024675
dbSNP: rs1205215998
Type: single nucleotide variant
Location: chr16:23635382 (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

pancreatic cancer, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group N hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

PALB2 p.Pro388Ser Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro388Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro388Thr Uncertain significance ★ ⚠ same residue
PALB2 p.Pro388fs Pathogenic ★★ same residue
PALB2 p.Pro388del Uncertain significance ★★ same residue
PALB2 p.Pro388dup Uncertain significance ★ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys 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-pro388 (accessed [today's date]).

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