Is BARD1 p.Arg43Pro (c.128G>C) pathogenic?

BARD1 p.Arg43Pro (c.128G>C) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.8321); Very rare (popmax 0.00133%, afr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BARD1 p.Arg43Pro (c.128G>C)?

BARD1 p.Arg43Pro (c.128G>C) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Arg43Pro (c.128G>C) in the general population?

BARD1 p.Arg43Pro (c.128G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

What do computational predictors say about BARD1 p.Arg43Pro (c.128G>C)?

AlphaMissense predicts likely pathogenic (score 0.8321) — an in-silico prediction, not a clinical call.

BARD1 p.Arg43Pro

c.128G>C · rs1060501305 · VCV495872

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.8321	likely pathogenic · top 10% in BARD1
REVEL	0.273	benign-leaning
SaProt	LLR -12.01	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	26.3	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 0.00133% African / African-American · 1/75,048 alleles

Overall 6.85e-05% 1/1,459,550 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.Arg43Pro
Coding: c.128G>C
MANE Select: NM_000465
dbSNP: rs1060501305
Type: single nucleotide variant
Location: chr2:214809442 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 43: an α-helix; the 'interaction with brca1' region

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

Disease context

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

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BARD1 p.Arg43Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43His Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Ser Uncertain significance ★★ ⚠ 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-arg43pro (accessed [today's date]).

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