Is BARD1 p.Ala90fs (c.268_270delinsCT) pathogenic?

BARD1 p.Ala90fs (c.268270delinsCT) is classified Pathogenic in BARD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ala90fs (c.268_270delinsCT)?

BARD1 p.Ala90fs (c.268_270delinsCT) is associated with hereditary neoplastic syndrome (ClinVar).

BARD1 p.Ala90fs

c.268_270delinsCT · VCV3260419

Pathogenic Single submitter

Classification

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	predicted	premature termination codon in exon 3 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.6, phastCons 1

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

Variant & gene context

Gene: BARD1
Protein: p.Ala90fs
Coding: c.268_270delinsCT
MANE Select: NM_000465
Type: Indel
Location: chr2:214792391 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 90: an α-helix; the 'interaction with brca1' region

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.Ala90_Trp91insTer Pathogenic ★★ same residue
BARD1 p.Ala90Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Ala90= Benign/Likely benign ★★ same residue
BARD1 p.Ala90Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Ala90Ser 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-ala90fs (accessed [today's date]).

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