Is PALB2 p.Ile730= (c.2190C>A) pathogenic?

PALB2 p.Ile730= (c.2190C>A) is classified Likely benign in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-01). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Ile730= (c.2190C>A)?

PALB2 p.Ile730= (c.2190C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Ile730= (c.2190C>A) in the general population?

PALB2 p.Ile730= (c.2190C>A) is absent from gnomAD v4.1 (gnomAD).

PALB2 p.Ile730=

c.2190C>A · rs958771546 · VCV1787416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.31	GERP -1.6, phastCons 0.001
Overall
CADD	6.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PALB2
Protein: p.Ile730=
Coding: c.2190C>A
MANE Select: NM_024675
dbSNP: rs958771546
Type: single nucleotide variant
Location: chr16:23629964 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 730: 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

Similar variants

PALB2 p.Ile730Met Uncertain significance ★ ⚠ same residue
PALB2 p.Ile730Val Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Ile730Thr 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
PALB2 p.Gln692Ter Likely pathogenic ★★★ same condition
PALB2 p.Glu3Ter 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-ile730 (accessed [today's date]).

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