Is BARD1 p.Ile764fs (c.2289dup) pathogenic?

BARD1 p.Ile764fs (c.2289dup) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-23). Very rare (popmax 0.000339%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ile764fs (c.2289dup)?

BARD1 p.Ile764fs (c.2289dup) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ile764fs (c.2289dup) in the general population?

BARD1 p.Ile764fs (c.2289dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

BARD1 p.Ile764fs

c.2289dup · rs1429930469 · VCV1789057

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

hereditary neoplastic syndrome

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	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 6.1	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,030 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,878 alleles · very rare

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.Ile764fs
Coding: c.2289dup
MANE Select: NM_000465
dbSNP: rs1429930469
Type: Duplication
Location: chr2:214728720 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 764: the brct 2 domain; an α-helix

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

Disease context

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

Also linked: hereditary breast carcinoma

Similar variants

BARD1 p.Ile764Met Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile764Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Ile764Val Uncertain significance ★ ⚠ same residue
BARD1 p.Ile764= Likely benign ★ same residue
BARD1 c.1395+1dup Likely pathogenic ★★ same condition
BARD1 p.Ala173fs Pathogenic ★★ same condition
BARD1 p.Ala200fs Pathogenic ★★ same condition
BARD1 p.Ala589fs 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-ile764fs (accessed [today's date]).

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