Is PALB2 p.Pro806= (c.2418G>A) pathogenic?

PALB2 p.Pro806= (c.2418G>A) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-02). Very rare (popmax 0.00891%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Pro806= (c.2418G>A)?

PALB2 p.Pro806= (c.2418G>A) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Pro806= (c.2418G>A) in the general population?

PALB2 p.Pro806= (c.2418G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

PALB2 p.Pro806=

c.2418G>A · rs577076372 · VCV183914

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, 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 3.2	GERP 0.55, phastCons 1
Overall
CADD	7.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,888 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00124% 20/1,614,140 alleles · very rare exomes 16/1,461,888 · genomes 4/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
South Asian	0.00769%	13,010
African / African-American	0.00266%	37,526
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000508%	196,672

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.Pro806=
Coding: c.2418G>A
MANE Select: NM_024675
dbSNP: rs577076372
Type: single nucleotide variant
Location: chr16:23629736 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 806: the 'required for interaction with polh and polh dna synthesis stimulation' region; 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.Pro806Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro806Gln Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro806Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro806Ser Uncertain significance ★ ⚠ same residue
PALB2 p.Pro806Thr 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

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-pro806 (accessed [today's date]).

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