Is BRCA2 p.Phe590fs (c.1766dup) pathogenic?

BRCA2 p.Phe590fs (c.1766dup) is classified Pathogenic in BRCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-07). No gnomAD frequency available for this variant; Associated with Fanconi anemia complementation group D1.

What condition is associated with BRCA2 p.Phe590fs (c.1766dup)?

BRCA2 p.Phe590fs (c.1766dup) is associated with Fanconi anemia complementation group D1, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Phe590fs (c.1766dup) in the general population?

BRCA2 p.Phe590fs (c.1766dup) is no gnomAD frequency available for this variant (gnomAD).

BRCA2 p.Phe590fs

Q: How is Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1766dup · rs2137474660 · VCV1439264

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi anemia complementation group D1

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 10 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -4.6, 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: BRCA2
Protein: p.Phe590fs
Coding: c.1766dup
MANE Select: NM_000059
dbSNP: rs2137474660
Type: Duplication
Location: chr13:32333242 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia complementation group D1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome medulloblastoma Wilms tumor 1 breast-ovarian cancer, familial, susceptibility to, 2 glioma susceptibility 3 pancreatic cancer, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma prostate cancer, hereditary

For Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations (Orphanet):

Inheritance: Autosomal recessive

Similar variants

BRCA2 p.Phe590Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Phe590Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.1448_1451dupCAGT Pathogenic ★★★ same condition
BRCA2 c.6081dupA Pathogenic ★★★ same condition
BRCA2 c.6396dupA Pathogenic ★★★ same condition
BRCA2 c.6528_6535dup Pathogenic ★★★ same condition
BRCA2 c.7806-2_7806-1dup Pathogenic ★★★ same condition
BRCA2 n.6325_6326insT 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/brca2-p-phe590fs (accessed [today's date]).

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