Is BARD1 p.Gln449= (c.1347A>G) pathogenic?

BARD1 p.Gln449= (c.1347A>G) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0512%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with BARD1 p.Gln449= (c.1347A>G)?

BARD1 p.Gln449= (c.1347A>G) is associated with Breast and/or ovarian cancer, hereditary neoplastic syndrome, familial ovarian cancer (ClinVar).

How common is BARD1 p.Gln449= (c.1347A>G) in the general population?

BARD1 p.Gln449= (c.1347A>G) is ultra-rare (popmax 0.0512%, nfe) (gnomAD).

BARD1 p.Gln449=

c.1347A>G · rs373257776 · VCV182027

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, nfe)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2.1, phastCons 0.91
Overall
CADD	5.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% European (non-Finnish) · 604/1,179,702 alleles

Filtering AF 0.0478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0465%

Overall 0.0398% 643/1,613,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0512%	1,953
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0224%	4,464
African / African-American	0.00666%	15,005

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.Gln449=
Coding: c.1347A>G
MANE Select: NM_000465
dbSNP: rs373257776
Type: single nucleotide variant
Location: chr2:214769280 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 449: an α-helix

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

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BARD1 p.Gln449Ter Pathogenic/Likely pathogenic ★★ same residue
BARD1 p.Gln449Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Gln449Glu Uncertain significance ★ ⚠ same residue
BARD1 p.Gln449Lys Uncertain significance ★ ⚠ same residue
BARD1 p.Gln449fs Pathogenic/Likely pathogenic ★★ 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-gln449 (accessed [today's date]).

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