Is BRCA2 p.Arg2336= (c.7008C>A) pathogenic?

BRCA2 p.Arg2336= (c.7008C>A) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-18). Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Arg2336= (c.7008C>A)?

BRCA2 p.Arg2336= (c.7008C>A) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Arg2336= (c.7008C>A) in the general population?

BRCA2 p.Arg2336= (c.7008C>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

BRCA2 p.Arg2336=

c.7008C>A · rs1555285975 · VCV531493

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,561,608)

Conditions

hereditary breast ovarian cancer 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 1.4	GERP 1.5, phastCons 1
Overall
CADD	6.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,561,608). 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.Arg2336=
Coding: c.7008C>A
MANE Select: NM_000059
dbSNP: rs1555285975
Type: single nucleotide variant
Location: chr13:32354861 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2336: a UniProt-annotated variant site (in fancd1; affects protein splicing and expression; decreases homologous recombination-mediated dna repair); a UniProt-annotated variant site (in); the 'interaction with hsf2bp' region

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

Disease context

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Arg2336His Pathogenic ★★★ ⚠ same residue
BRCA2 p.Arg2336Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
BRCA2 p.Arg2336Pro Pathogenic/Likely pathogenic ★★ ⚠ same residue
BRCA2 p.Arg2336Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg2336fs Pathogenic ★★★ same residue
BRCA2 p.Arg2336Gly Likely benign ★ same residue
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A 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-arg2336 (accessed [today's date]).

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