Is BARD1 p.Pro657fs (c.1970del) pathogenic?

BARD1 p.Pro657fs (c.1970del) is classified Pathogenic/Likely pathogenic in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-24). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Pro657fs (c.1970del)?

BARD1 p.Pro657fs (c.1970del) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Pro657fs (c.1970del) in the general population?

BARD1 p.Pro657fs (c.1970del) is absent from gnomAD (gnomAD).

BARD1 p.Pro657fs

c.1970del · rs786203739 · VCV187445

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

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.
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, 31 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 -2.4	GERP -3.9

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

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.Pro657fs
Coding: c.1970del
MANE Select: NM_000465
dbSNP: rs786203739
Type: Deletion
Location: chr2:214730442 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 657: an α-helix

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.Pro657_Arg658delinsArgProCys Uncertain significance ★★ same residue
BARD1 p.Pro657Gln Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro657Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro657Thr Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro657= Likely benign ★ same residue
BARD1 c.1306_1314+7del Likely pathogenic ★★ same condition
BARD1 c.158+2_158+10del Likely pathogenic ★★ same condition
BARD1 c.1676_1677+23del 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-pro657fs (accessed [today's date]).

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