Is BRCA1 p.Pro209fs (c.626del) pathogenic?

BRCA1 p.Pro209fs (c.626del) is classified Uncertain significance in BRCA1 (ClinVar, Expert panel, 6 submitters; last evaluated 2026-08-27). Absent from gnomAD; Associated with BRCA1-related cancer predisposition.

What condition is associated with BRCA1 p.Pro209fs (c.626del)?

BRCA1 p.Pro209fs (c.626del) is associated with BRCA1-related cancer predisposition, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Pro209fs (c.626del) in the general population?

BRCA1 p.Pro209fs (c.626del) is absent from gnomAD (gnomAD).

BRCA1 p.Pro209fs

c.626del · rs886040920 · VCV267609

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BRCA1-related cancer predisposition

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 9 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.3	GERP -2.5, phastCons 0.52

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.

ClinGen expert panel

Uncertain Significance — ENIGMA BRCA1 and BRCA2 VCEP (BRCA1-related cancer predisposition).

Variant & gene context

Gene: BRCA1
Protein: p.Pro209fs
Coding: c.626del
MANE Select: NM_007294
dbSNP: rs886040920
Type: Deletion
Location: chr17:43095890 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome

Similar variants

BRCA1 p.Pro209Ser Uncertain significance ★★ ⚠ same residue
BRCA1 p.Pro209= Likely benign ★★ same residue
BRCA1 p.Pro209Ala Uncertain significance ★ ⚠ same residue
BRCA1 p.Pro209Arg Uncertain significance ★ ⚠ same residue
BRCA1 p.Pro209Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro209Thr Uncertain significance ★ same residue
BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.4358_4484del 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/brca1-p-pro209fs (accessed [today's date]).

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