Is BARD1 p.Arg112Pro (c.335G>C) pathogenic?

BARD1 p.Arg112Pro (c.335G>C) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely pathogenic (0.7908); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Arg112Pro (c.335G>C)?

BARD1 p.Arg112Pro (c.335G>C) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Arg112Pro (c.335G>C) in the general population?

BARD1 p.Arg112Pro (c.335G>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

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

What do computational predictors say about BARD1 p.Arg112Pro (c.335G>C)?

AlphaMissense predicts likely pathogenic (score 0.7908) — an in-silico prediction, not a clinical call.

BARD1 p.Arg112Pro

c.335G>C · rs587781591 · VCV221102

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7908 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.7908	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -15.77	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.075	GERP -0.95
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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.Arg112Pro
Coding: c.335G>C
MANE Select: NM_000465
dbSNP: rs587781591
Type: single nucleotide variant
Location: chr2:214792326 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 112: 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 carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BARD1 p.Arg112Ter Pathogenic/Likely pathogenic ★★ same residue
BARD1 p.Arg112Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg112= Benign/Likely benign ★★ same residue
BARD1 p.Arg112Gln Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg112pro (accessed [today's date]).

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