Is PALB2 p.Phe606fs (c.1817_1818del) pathogenic?

PALB2 p.Phe606fs (c.18171818del) is classified Pathogenic in PALB2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-16). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Phe606fs (c.1817_1818del)?

PALB2 p.Phe606fs (c.1817_1818del) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Phe606fs (c.1817_1818del) in the general population?

PALB2 p.Phe606fs (c.1817_1818del) is absent from gnomAD (gnomAD).

PALB2 p.Phe606fs

c.1817_1818del · rs1060499818 · VCV402295

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 0.87, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PALB2
Protein: p.Phe606fs
Coding: c.1817_1818del
MANE Select: NM_024675
dbSNP: rs1060499818
Type: Deletion
Location: chr16:23630336 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 606: a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5); an α-helix

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.Phe606= Benign/Likely benign ★★ same residue
PALB2 p.Glu178fs Pathogenic ★★★ same condition
PALB2 p.Gly1121fs Likely pathogenic ★★★ same condition
PALB2 p.Leu531fs Pathogenic ★★★ same condition
PALB2 p.Ser172fs Pathogenic ★★★ same condition
PALB2 p.Leu1171fs Uncertain significance ★★★ same condition
PALB2 p.Phe1181fs Uncertain significance ★★★ same condition
PALB2 c.1686del Pathogenic/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-phe606fs (accessed [today's date]).

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