Is BARD1 p.Asp94Ala (c.281A>C) pathogenic?

BARD1 p.Asp94Ala (c.281A>C) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). AlphaMissense: likely pathogenic (0.8856); Ultra-rare (popmax 0.0167%, amr); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Asp94Ala (c.281A>C)?

BARD1 p.Asp94Ala (c.281A>C) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Asp94Ala (c.281A>C) in the general population?

BARD1 p.Asp94Ala (c.281A>C) is ultra-rare (popmax 0.0167%, amr) (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.Asp94Ala (c.281A>C)?

AlphaMissense predicts likely pathogenic (score 0.8856) — an in-silico prediction, not a clinical call.

BARD1 p.Asp94Ala

c.281A>C · rs757569689 · VCV230637

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.8856	likely pathogenic · top 8% in BARD1
REVEL	0.696	pathogenic-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	24.9	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 0.0167% Admixed American · 10/59,860 alleles

Filtering AF 0.00902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00683%

Overall 0.000868% 14/1,612,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,986
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.000254%	393,224

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.Asp94Ala
Coding: c.281A>C
MANE Select: NM_000465
dbSNP: rs757569689
Type: single nucleotide variant
Location: chr2:214792380 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 94: 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.Asp94Asn Uncertain significance ★ ⚠ same residue
BARD1 p.Asp94Glu Uncertain significance ★ ⚠ same residue
BARD1 p.Asp94= Likely benign ★ same residue
BARD1 p.Asp94_Leu95insTer 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-asp94ala (accessed [today's date]).

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