Is BARD1 p.Val154fs (c.457_460dup) pathogenic?

BARD1 p.Val154fs (c.457460dup) is classified Pathogenic in BARD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-20). Very rare (popmax 0.00134%, afr); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Val154fs (c.457_460dup)?

BARD1 p.Val154fs (c.457_460dup) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Val154fs (c.457_460dup) in the general population?

BARD1 p.Val154fs (c.457_460dup) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

BARD1 p.Val154fs

c.457_460dup · rs772486760 · VCV230344

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hereditary breast carcinoma

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1
Overall
CADD	33.0	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 0.00134% African / African-American · 1/74,850 alleles

Overall 0.000658% 1/151,968 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.Val154fs
Coding: c.457_460dup
MANE Select: NM_000465
dbSNP: rs772486760
Type: Duplication
Location: chr2:214781413 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB

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

Disease context

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BARD1 p.Val154= Likely benign ★★ same residue
BARD1 p.Val154Phe Uncertain significance ★ ⚠ 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
BARD1 p.Asn450fs Pathogenic/Likely pathogenic ★★ same condition
BARD1 p.Asn549fs 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-val154fs (accessed [today's date]).

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