Is BARD1 p.Gln730Ter (c.2188C>T) pathogenic?

BARD1 p.Gln730Ter (c.2188C>T) is classified Pathogenic/Likely pathogenic in BARD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-13). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Gln730Ter (c.2188C>T)?

BARD1 p.Gln730Ter (c.2188C>T) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Gln730Ter (c.2188C>T) in the general population?

BARD1 p.Gln730Ter (c.2188C>T) is absent from gnomAD v4.1 (gnomAD).

BARD1 p.Gln730Ter

c.2188C>T · rs1559372004 · VCV2565192

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	48.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BARD1
Protein: p.Gln730Ter
Coding: c.2188C>T
MANE Select: NM_000465
dbSNP: rs1559372004
Type: single nucleotide variant
Location: chr2:214728822 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 730: the brct 2 domain; 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.Gln730Glu Uncertain significance ★★ ⚠ same residue
BARD1 p.Gln730Lys Uncertain significance ★★ ⚠ same residue
BARD1 p.Gln730Pro Uncertain significance ★★ ⚠ same residue
BARD1 p.Gln730Arg Uncertain significance ★ ⚠ same residue
BARD1 p.Gln730= Likely benign ★ same residue
BARD1 c.1314+1G>A Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.1314+1G>T Likely pathogenic ★★ same condition
BARD1 c.1396-1G>A 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-gln730ter (accessed [today's date]).

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