Is PALB2 p.Ser1102fs (c.3305_3306insACGCTCAG) pathogenic?

PALB2 p.Ser1102fs (c.33053306insACGCTCAG) is classified Pathogenic in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Ser1102fs (c.3305_3306insACGCTCAG)?

PALB2 p.Ser1102fs (c.3305_3306insACGCTCAG) is associated with hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Ser1102fs (c.3305_3306insACGCTCAG) in the general population?

PALB2 p.Ser1102fs (c.3305_3306insACGCTCAG) is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

PALB2 p.Ser1102fs

c.3305_3306insACGCTCAG · rs2142272095 · VCV1455890

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 44 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.011	GERP -3.7

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.Ser1102fs
Coding: c.3305_3306insACGCTCAG
MANE Select: NM_024675
dbSNP: rs2142272095
Type: Insertion
Location: chr16:23607908 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 1102: a β-strand; the 'required for interaction with polh and polh dna synthesis stimulation' region; the 'interaction with rad51, brca2 and polh' region; a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5); a UniProt-annotated variant site (risk factor for brovca5; risk factor for pnca3)

Full PALB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

PALB2 p.Ser1102Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser1102= Benign/Likely benign ★★ same residue
PALB2 p.Ser1102Ile Uncertain significance ★ ⚠ same residue
PALB2 p.Ala406_Glu407insTer Pathogenic ★★ same condition
PALB2 p.Arg476Ter Pathogenic ★★ same condition
PALB2 p.Asn349fs Pathogenic ★★ same condition
PALB2 p.Cys886fs Pathogenic ★★ same condition
PALB2 p.Gln260fs 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-ser1102fs (accessed [today's date]).

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