Is BRCA2 p.Phe2200del (c.6599_6601del) pathogenic?

BRCA2 p.Phe2200del (c.65996601del) is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-11). Very rare (popmax 0.00134%, afr); Associated with hereditary breast carcinoma.

What condition is associated with BRCA2 p.Phe2200del (c.6599_6601del)?

BRCA2 p.Phe2200del (c.6599_6601del) is associated with hereditary breast carcinoma, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Phe2200del (c.6599_6601del) in the general population?

BRCA2 p.Phe2200del (c.6599_6601del) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Hereditary breast cancer inherited?

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

BRCA2 p.Phe2200del

c.6599_6601del · rs80359607 · VCV2680244

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hereditary breast carcinoma

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 -0.55	GERP -0.61

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,640 alleles

Overall 6.21e-05% 1/1,609,214 alleles · very rare exomes 1/1,456,934 · genomes 0/152,280 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA2
Protein: p.Phe2200del
Coding: c.6599_6601del
MANE Select: NM_000059
dbSNP: rs80359607
Type: Deletion
Location: chr13:32340952 (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

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

Also linked: breast-ovarian cancer, familial, susceptibility to, 2

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRCA2 p.Phe2200_Ser2201insTer Pathogenic ★★★ same residue
BRCA2 p.Phe2200Ser Conflicting classifications of pathogenicity ★ same residue
BRCA2 c.316+4del Pathogenic ★★★ same condition
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del Pathogenic ★★★ same condition
BRCA2 c.7008-?_7805+?del Pathogenic ★★★ same condition
BRCA2 c.7980_7984delTGATA Pathogenic ★★★ same condition
BRCA2 c.8312del 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-phe2200del (accessed [today's date]).

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