Is BRCA1 c.5408delG pathogenic?

BRCA1 c.5408delG is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). Very rare (popmax 6.84e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 c.5408delG?

BRCA1 c.5408delG is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 c.5408delG in the general population?

BRCA1 c.5408delG is very rare (popmax 6.84e-05%) (gnomAD).

BRCA1 c.5408delG

rs2546718821 · VCV2585830

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

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 · substitutions only
Constraint at this position
Conservation	phyloP -0.005	GERP -4.9
Non-coding constraint	Z 1.94	1 kb window · o/e 0.85 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,864 alleles · very rare

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: BRCA1
Coding: c.5408delG
MANE Select: NM_007294
dbSNP: rs2546718821
Type: Deletion
Location: chr17:43047702 (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

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

Similar variants

BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same condition
BRCA1 c.5333-36_5406+400del Pathogenic ★★★ same condition
BRCA1 c.5470_5477del Pathogenic ★★★ same condition
BRCA1 p.Ala1142fs Pathogenic ★★★ same condition
BRCA1 p.Ala433fs Pathogenic ★★★ same condition
BRCA1 p.Ala439_Leu440insTer 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-c-5408delg (accessed [today's date]).

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