Is BRCA2 p.Pro3300= (c.9900A>C) pathogenic?

BRCA2 p.Pro3300= (c.9900A>C) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-10-03). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Pro3300= (c.9900A>C)?

BRCA2 p.Pro3300= (c.9900A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Pro3300= (c.9900A>C) in the general population?

BRCA2 p.Pro3300= (c.9900A>C) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Pro3300=

c.9900A>C · rs1593201999 · VCV801130

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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 -2.5	GERP -2.8
Overall
CADD	2.21	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: BRCA2
Protein: p.Pro3300=
Coding: c.9900A>C
MANE Select: NM_000059
dbSNP: rs1593201999
Type: single nucleotide variant
Location: chr13:32398413 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3300: a UniProt-annotated variant site (in one patient with esophageal carcinoma); the 'tr2 region' region; an α-helix

Full BRCA2 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

BRCA2 p.Pro3300Ser Uncertain significance ★★ ⚠ same residue
BRCA2 p.Pro3300Thr Uncertain significance ★★ ⚠ same residue
BRCA2 p.Pro3300Gln Uncertain significance ★ ⚠ same residue
BRCA2 p.Pro3300Leu Uncertain significance ★ ⚠ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C 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-pro3300 (accessed [today's date]).

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