Is BARD1 p.Met768Ter (c.2300_2301dup) pathogenic?

BARD1 p.Met768Ter (c.23002301dup) is classified Pathogenic in BARD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-25). Ultra-rare (gnomAD MAF 1.341e-05); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Met768Ter (c.2300_2301dup)?

BARD1 p.Met768Ter (c.2300_2301dup) is associated with hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Met768Ter (c.2300_2301dup) in the general population?

BARD1 p.Met768Ter (c.2300_2301dup) is ultra-rare (gnomAD MAF 1.341e-05) (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.Met768Ter

c.2300_2301dup · rs750413473 · VCV2583691

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.341e-05)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP 0.77, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.00134% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BARD1
Protein: p.Met768Ter
Coding: c.2300_2301dup
MANE Select: NM_000465
dbSNP: rs750413473
Type: Microsatellite
Location: chr2:214728708 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 768: the brct 2 domain; an α-helix

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

For Hereditary breast cancer (Orphanet):

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

Similar variants

BARD1 p.Met768Ile Uncertain significance ★ ⚠ same residue
BARD1 p.Met768Lys Uncertain significance ★ ⚠ same residue
BARD1 p.Met768Thr Uncertain significance ★ ⚠ same residue
BARD1 p.Arg194fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Glu287fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Glu59fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.His325fs Pathogenic ★★ same condition
BARD1 p.Ser179_Tyr180insTer 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-met768ter (accessed [today's date]).

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