Is PALB2 p.Pro358Phe (c.1072_1073delinsTT) pathogenic?

PALB2 p.Pro358Phe (c.10721073delinsTT) is classified Uncertain significance in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Pro358Phe (c.1072_1073delinsTT)?

PALB2 p.Pro358Phe (c.1072_1073delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Pro358Phe (c.1072_1073delinsTT) in the general population?

PALB2 p.Pro358Phe (c.1072_1073delinsTT) is no gnomAD frequency available for this variant (gnomAD).

PALB2 p.Pro358Phe

c.1072_1073delinsTT · rs1966996117 · VCV920879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -0.5, phastCons 0.96
Regional constraint	o/e 1.00	unconstrained · MANE · 38 kb · p 0.87 · regional, not allelic

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.Pro358Phe
Coding: c.1072_1073delinsTT
MANE Select: NM_024675
dbSNP: rs1966996117
Type: Indel
Location: chr16:23635473 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 358: the 'disordered' 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

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

Similar variants

PALB2 p.Pro358fs Pathogenic ★★ same residue
PALB2 p.Pro358His Uncertain significance ★★ ⚠ same residue
PALB2 p.Pro358Arg Uncertain significance ★ ⚠ same residue
PALB2 p.Pro358Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro358Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Pro358= Likely benign ★ same residue
PALB2 p.Ala842fs Pathogenic ★★★ same condition
PALB2 c.2223_2224delinsG 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-pro358phe (accessed [today's date]).

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