Is BARD1 p.Lys596= (c.1788A>G) pathogenic?

BARD1 p.Lys596= (c.1788A>G) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0567%, amr); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Lys596= (c.1788A>G)?

BARD1 p.Lys596= (c.1788A>G) is associated with BARD1-related cancer predisposition, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Lys596= (c.1788A>G) in the general population?

BARD1 p.Lys596= (c.1788A>G) is ultra-rare (popmax 0.0567%, amr) (gnomAD).

BARD1 p.Lys596=

c.1788A>G · rs777084777 · VCV215747

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0567%, amr)

Conditions

BARD1-related cancer predisposition

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	GERP -3.9, phastCons 0.001
Overall
CADD	3.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0567% Admixed American · 34/59,994 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00242% 39/1,613,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0567%	1,765
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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.Lys596=
Coding: c.1788A>G
MANE Select: NM_000465
dbSNP: rs777084777
Type: single nucleotide variant
Location: chr2:214745744 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 596: the brct 1 domain; a β-strand

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

Disease context

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Lys596Asn Uncertain significance ★ ⚠ same residue
BARD1 p.Lys596Gln Uncertain significance ★ ⚠ same residue
BARD1 p.Lys596fs Pathogenic ★★ 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
BARD1 c.1396-1G>C Likely pathogenic ★★ same condition
BARD1 c.1396-1G>T 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-lys596 (accessed [today's date]).

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