Is BARD1 p.Val767fs (c.2300_2301del) pathogenic?

BARD1 p.Val767fs (c.23002301del) is classified Pathogenic/Likely pathogenic in BARD1 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-05-08). Very rare (popmax 0.00229%, nfe); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Val767fs (c.2300_2301del)?

BARD1 p.Val767fs (c.2300_2301del) is associated with BARD1-related cancer predisposition, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Val767fs (c.2300_2301del) in the general population?

BARD1 p.Val767fs (c.2300_2301del) is very rare (popmax 0.00229%, nfe) (gnomAD).

BARD1 p.Val767fs

c.2300_2301del · rs750413473 · VCV230523

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Conditions

BARD1-related cancer predisposition

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 1.9	GERP 0.77, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,022 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00235% 38/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,674
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)grpmax	0.00229%	43,705

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val767fs
Coding: c.2300_2301del
MANE Select: NM_000465
dbSNP: rs750413473
Type: Microsatellite
Location: chr2:214728709 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 767: the brct 2 domain; an α-helix

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

Disease context

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Val767Met Uncertain significance ★★ ⚠ same residue
BARD1 p.Val767= Benign/Likely benign ★★ same residue
BARD1 p.Val767Ala Uncertain significance ★ ⚠ same residue
BARD1 p.Val767Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Arg194fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Glu287fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Glu59fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.His325fs 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-val767fs (accessed [today's date]).

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