Is BARD1 p.Ile653fs (c.1957dup) pathogenic?

BARD1 p.Ile653fs (c.1957dup) is classified Likely pathogenic in BARD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ile653fs (c.1957dup)?

BARD1 p.Ile653fs (c.1957dup) is associated with hereditary neoplastic syndrome (ClinVar).

BARD1 p.Ile653fs

c.1957dup · VCV4842584

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 within the last 50 nt of the penultimate exon (10 of 11, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1

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

Variant & gene context

Gene: BARD1
Protein: p.Ile653fs
Coding: c.1957dup
MANE Select: NM_000465
Type: Duplication
Location: chr2:214730454 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 653: the brct 1 domain

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

Similar variants

BARD1 p.Ile653Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile653= Likely benign ★★ same residue
BARD1 p.Ile653Thr Uncertain significance ★ ⚠ same residue
BARD1 c.1395+1dup Likely pathogenic ★★ same condition
BARD1 p.Ala173fs Pathogenic ★★ same condition
BARD1 p.Asn450fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Asn549fs Pathogenic ★★ same condition
BARD1 p.Asn744Ter 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-ile653fs (accessed [today's date]).

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