Is BARD1 p.Ala283Pro (c.847G>C) pathogenic?

BARD1 p.Ala283Pro (c.847G>C) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-28). AlphaMissense: likely benign (0.1782); Very rare (popmax 0.00416%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Ala283Pro (c.847G>C)?

BARD1 p.Ala283Pro (c.847G>C) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Ala283Pro (c.847G>C) in the general population?

BARD1 p.Ala283Pro (c.847G>C) is very rare (popmax 0.00416%, nfe) (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.Ala283Pro (c.847G>C)?

AlphaMissense predicts likely benign (score 0.1782) — an in-silico prediction, not a clinical call.

BARD1 p.Ala283Pro

c.847G>C · rs923851371 · VCV482764

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00416%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.1782	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00416% European (non-Finnish) · 49/1,179,206 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00342% 50/1,459,972 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00416%	24,065
Remaining individualsnot grpmax-eligible	0.0016%	62,392

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.Ala283Pro
Coding: c.847G>C
MANE Select: NM_000465
dbSNP: rs923851371
Type: single nucleotide variant
Location: chr2:214781027 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB

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.Ala283Thr Uncertain significance ★★ ⚠ same residue
BARD1 p.Ala283Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Ala283= Benign ★ same residue
BARD1 p.Ala283fs 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
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-ala283pro (accessed [today's date]).

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