Is PALB2 p.Gln613= (c.1839G>A) pathogenic?

PALB2 p.Gln613= (c.1839G>A) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-10). Ultra-rare (popmax 0.0356%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Gln613= (c.1839G>A)?

PALB2 p.Gln613= (c.1839G>A) is associated with hereditary neoplastic syndrome, familial pancreatic carcinoma, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Gln613= (c.1839G>A) in the general population?

PALB2 p.Gln613= (c.1839G>A) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

PALB2 p.Gln613=

c.1839G>A · rs199682414 · VCV215928

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

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 0.28	GERP 0.88, phastCons 0.98
Overall
CADD	7.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0356% East Asian · 16/44,888 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0013% 21/1,614,178 alleles · ultra-rare exomes 17/1,461,884 · genomes 4/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	8.47e-05%	1,180,038

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.Gln613=
Coding: c.1839G>A
MANE Select: NM_024675
dbSNP: rs199682414
Type: single nucleotide variant
Location: chr16:23630315 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 613: 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: familial pancreatic carcinoma hereditary breast carcinoma

Similar variants

PALB2 p.Gln613Ter Pathogenic ★★ same residue
PALB2 p.Gln613Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.Gln613Glu Uncertain significance ★★ ⚠ same residue
PALB2 p.Gln613Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Gln613fs 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-gln613 (accessed [today's date]).

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