Is PALB2 p.Lys437= (c.1311A>G) pathogenic?

PALB2 p.Lys437= (c.1311A>G) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0977%, sas); Associated with pancreatic cancer, susceptibility to, 3.

What condition is associated with PALB2 p.Lys437= (c.1311A>G)?

PALB2 p.Lys437= (c.1311A>G) is associated with pancreatic cancer, susceptibility to, 3, Fanconi anemia complementation group N, hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Lys437= (c.1311A>G) in the general population?

PALB2 p.Lys437= (c.1311A>G) is ultra-rare (popmax 0.0977%, sas) (gnomAD).

PALB2 p.Lys437=

c.1311A>G · rs190489275 · VCV184531

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0977%, sas)

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 0.092	GERP -3.4, phastCons 0.93
Overall
CADD	3.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0977% South Asian · 89/91,080 alleles

Filtering AF 0.0812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.00632% 102/1,614,196 alleles · ultra-rare exomes 99/1,461,850 · genomes 3/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0977%	1,023
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.000593%	168,578

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.Lys437=
Coding: c.1311A>G
MANE Select: NM_024675
dbSNP: rs190489275
Type: single nucleotide variant
Location: chr16:23635235 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 437: the 'cham (chromatin-association motif); required for chromatin association, mediates nucleosome association' region; 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 breast-ovarian cancer, familial, susceptibility to, 5

Similar variants

PALB2 p.Lys437Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.Lys437Glu Uncertain significance ★★ ⚠ same residue
PALB2 p.Lys437Gln 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
PALB2 p.Gln692Ter Likely pathogenic ★★★ same condition
PALB2 p.Glu3Ter 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-lys437 (accessed [today's date]).

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