Is BARD1 p.Arg751Gln (c.2252G>A) pathogenic?

BARD1 p.Arg751Gln (c.2252G>A) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.2803); Ultra-rare (popmax 0.011%, sas); Associated with Breast and/or ovarian cancer.

What condition is associated with BARD1 p.Arg751Gln (c.2252G>A)?

BARD1 p.Arg751Gln (c.2252G>A) is associated with Breast and/or ovarian cancer, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Arg751Gln (c.2252G>A) in the general population?

BARD1 p.Arg751Gln (c.2252G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about BARD1 p.Arg751Gln (c.2252G>A)?

AlphaMissense predicts likely benign (score 0.2803) — an in-silico prediction, not a clinical call.

BARD1 p.Arg751Gln

c.2252G>A · rs587782246 · VCV142117

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.2803 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.2803	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -10.14	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,084 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00626% 101/1,614,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
European (non-Finnish)	0.00712%	14,048
East Asian	0.00446%	22,446
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Admixed American	0.00167%	59,992
Finnishnot grpmax-eligible	0.00156%	64,034
African / African-American	0.00133%	74,912

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.Arg751Gln
Coding: c.2252G>A
MANE Select: NM_000465
dbSNP: rs587782246
Type: single nucleotide variant
Location: chr2:214728758 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 751: the brct 2 domain; a β-strand

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 hereditary breast carcinoma

Similar variants

BARD1 p.Arg751Pro Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg751Trp Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg751= 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
BARD1 c.1396-1G>C Likely pathogenic ★★ same condition
BARD1 c.1396-1G>T 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-arg751gln (accessed [today's date]).

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