Is BARD1 p.Arg565= (c.1695T>C) pathogenic?

BARD1 p.Arg565= (c.1695T>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0285%, sas); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Arg565= (c.1695T>C)?

BARD1 p.Arg565= (c.1695T>C) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Arg565= (c.1695T>C) in the general population?

BARD1 p.Arg565= (c.1695T>C) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

How is Hereditary breast cancer inherited?

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

BARD1 p.Arg565=

c.1695T>C · rs569636814 · VCV414108

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.2
Overall
CADD	0.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,088 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00192% 31/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.00167%	60,012

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
Protein: p.Arg565=
Coding: c.1695T>C
MANE Select: NM_000465
dbSNP: rs569636814
Type: single nucleotide variant
Location: chr2:214745837 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 565: the brct 1 domain

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

Disease context

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BARD1 p.Arg565Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg565Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg565Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Arg565His Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Arg565Ser Uncertain significance ★ ⚠ same residue
BARD1 c.1314+1G>A Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.1314+1G>T Likely pathogenic ★★ same condition
BARD1 c.1396-1G>A 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-p-arg565 (accessed [today's date]).

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