Is BARD1 p.Pro759Ile (c.2275_2276delinsAT) pathogenic?

BARD1 p.Pro759Ile (c.22752276delinsAT) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-09). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Pro759Ile (c.2275_2276delinsAT)?

BARD1 p.Pro759Ile (c.2275_2276delinsAT) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Pro759Ile (c.2275_2276delinsAT) in the general population?

BARD1 p.Pro759Ile (c.2275_2276delinsAT) is absent from gnomAD (gnomAD).

BARD1 p.Pro759Ile

c.2275_2276delinsAT · rs1692195261 · VCV992588

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic

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.Pro759Ile
Coding: c.2275_2276delinsAT
MANE Select: NM_000465
dbSNP: rs1692195261
Type: Indel
Location: chr2:214728734 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 759: the brct 2 domain; a β-strand

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.Pro759Ala Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro759Ser Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro759= Benign/Likely benign ★★ same residue
BARD1 p.Pro759His Uncertain significance ★ same residue
BARD1 p.Pro759Thr Uncertain significance ★ ⚠ same residue
BARD1 p.Ala25fs Pathogenic ★★ same condition
BARD1 p.Arg378fs Pathogenic ★★ same condition
BARD1 p.Glu317fs 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-pro759ile (accessed [today's date]).

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