Is BARD1 c.2001+66A>C pathogenic?

BARD1 c.2001+66A>C is classified Benign in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-04-19). Common (popmax 12%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BARD1 c.2001+66A>C?

BARD1 c.2001+66A>C is associated with hereditary breast ovarian cancer syndrome (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.

BARD1 c.2001+66A>C

Q: How common is BARD1 c.2001+66A>C in the general population?

BARD1 c.2001+66A>C is common (popmax 12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs75237746 · VCV1291071

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +66	deep intronic (+66 nt into the intron)
SpliceAI	Δ0.35	donor loss, 28 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.051	GERP -4.2
Non-coding constraint	Z 0.88	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12% African / African-American · 8,466/70,766 alleles

Filtering AF 11.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.7%

Overall 4.79% 67,932/1,417,652 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12%	8
Middle Eastern	6.53%	15
Ashkenazi Jewishnot grpmax-eligible	5.43%	18
Remaining individualsnot grpmax-eligible	5.27%	19
European (non-Finnish)	4.99%	20
Amishnot grpmax-eligible	4.82%	21
Admixed American	3.36%	30
Finnishnot grpmax-eligible	1.96%	51
South Asian	1.52%	66
East Asian	0.0137%	7,312

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: BARD1
Coding: c.2001+66A>C
MANE Select: NM_000465
dbSNP: rs75237746
Type: single nucleotide variant
Location: chr2:214730345 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB

Full BARD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — 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

BARD1 c.1314+1G>A Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.159-1G>A Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.159-1G>T Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.1811-1G>A Likely pathogenic ★★ same condition
BARD1 c.216-2A>G Likely pathogenic ★★ same condition
BARD1 p.Arg150Ter Pathogenic ★★ same condition
BARD1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Arg641Ter Pathogenic/Likely 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/bard1-c-2001-plus-66a-c (accessed [today's date]).

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