Is BRCA1 c.4185+112C>A pathogenic?

BRCA1 c.4185+112C>A is classified Benign in BRCA1 (ClinVar, Expert panel, 3 submitters; last evaluated 2015-01-12). Common (popmax 27.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 c.4185+112C>A?

BRCA1 c.4185+112C>A is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

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

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

BRCA1 c.4185+112C>A

Q: How common is BRCA1 c.4185+112C>A in the general population?

BRCA1 c.4185+112C>A is common (popmax 27.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2070833 · VCV209443

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 27.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +112	deep intronic (+112 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.2, phastCons 0.001
Non-coding constraint	Z 2.10	1 kb window · o/e 0.84 · regional · uncalibrated
Overall
CADD	2.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.7% East Asian · 10,676/38,536 alleles

Filtering AF 27.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.1%

Overall 2.33% 23,409/1,003,540 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	27.7%	4
Admixed American	15.4%	6
Finnishnot grpmax-eligible	3.93%	25
Remaining individualsnot grpmax-eligible	2.54%	39
Ashkenazi Jewishnot grpmax-eligible	1.51%	66
South Asian	0.842%	119
Middle Eastern	0.304%	329
African / African-American	0.22%	454
European (non-Finnish)	0.138%	723

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.4185+112C>A
MANE Select: NM_007294
dbSNP: rs2070833
Type: single nucleotide variant
Location: chr17:43090832 (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

breast-ovarian cancer, familial, susceptibility to, 1 — 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

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-4185-plus-112c-a (accessed [today's date]).

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