BRCA1 c.5406+9T>C
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
3
Breast and/or ovarian cancer
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +9 | near-intronic (+9 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.45 | GERP -2.8 |
| Non-coding constraint | Z 1.37 | 1 kb window · o/e 0.89 · regional · uncalibrated |
| Overall | ||
| CADD | 4.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,988 alleles
Overall
0.000137%
2/1,460,778 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,988 |
| European (non-Finnish) | 8.48e-05% | 1,179,058 |
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.5406+9T>C
- MANE Select
- NM_007294
- dbSNP
- rs80358040
- Type
- single nucleotide variant
- Location
- chr17:43049112 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
Similar variants
- BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
- BRCA1 c.135-1G>T Pathogenic ★★★ same condition
- BRCA1 c.212+1G>A Pathogenic ★★★ same condition
- BRCA1 c.212+1G>T Pathogenic ★★★ same condition
- BRCA1 c.212+3A>G Pathogenic ★★★ same condition
- BRCA1 c.213-12A>G Pathogenic ★★★ same condition
- BRCA1 c.213-15A>G Likely pathogenic ★★★ same condition
- BRCA1 c.302-1G>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/brca1-c-5406-plus-9t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown