Is BARD1 p.Ile249fs (c.745dup) pathogenic?

BARD1 p.Ile249fs (c.745dup) is classified Pathogenic in BARD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-25). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Ile249fs (c.745dup)?

BARD1 p.Ile249fs (c.745dup) is associated with hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ile249fs (c.745dup) in the general population?

BARD1 p.Ile249fs (c.745dup) is absent from gnomAD (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.Ile249fs

c.745dup · rs1553622487 · VCV406757

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.31	GERP -4.5

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BARD1
Protein: p.Ile249fs
Coding: c.745dup
MANE Select: NM_000465
dbSNP: rs1553622487
Type: Duplication
Location: chr2:214781128 (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 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.Ile249Thr Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile249= Benign/Likely benign ★★ same residue
BARD1 p.Ile249Ser Uncertain significance ★ ⚠ same residue
BARD1 p.Ile249Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Ala173fs Pathogenic ★★ same condition
BARD1 p.Ala200fs Pathogenic ★★ same condition
BARD1 p.Ala589fs Pathogenic ★★ same condition
BARD1 p.Asn450fs 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-p-ile249fs (accessed [today's date]).

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