Is BARD1 p.Cys53Tyr (c.158G>A) pathogenic?

BARD1 p.Cys53Tyr (c.158G>A) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.9253); Very rare (popmax 0.00223%, eas); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Cys53Tyr (c.158G>A)?

BARD1 p.Cys53Tyr (c.158G>A) is associated with hereditary breast carcinoma, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Cys53Tyr (c.158G>A) in the general population?

BARD1 p.Cys53Tyr (c.158G>A) is very rare (popmax 0.00223%, eas) (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.Cys53Tyr (c.158G>A)?

AlphaMissense predicts likely pathogenic (score 0.9253) — an in-silico prediction, not a clinical call.

BARD1 p.Cys53Tyr

c.158G>A · rs747582517 · VCV460712

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.9253	likely pathogenic · top 5% in BARD1
REVEL	0.815	moderately pathogenic-leaning
SaProt	LLR -17.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.86	donor loss · deltas
Pangolin	Δ0.72	loss · gain 0.70 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	36.0	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 0.00223% East Asian · 1/44,838 alleles

Overall 0.000137% 2/1,460,120 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,838
European (non-Finnish)	8.48e-05%	1,179,834

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.Cys53Tyr
Coding: c.158G>A
MANE Select: NM_000465
dbSNP: rs747582517
Type: single nucleotide variant
Location: chr2:214809412 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 53: a turn; 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 breast ovarian cancer syndrome hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

BARD1 p.Cys53Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Cys53= Conflicting classifications of pathogenicity ★ same residue
BARD1 p.Cys53Ser Uncertain significance ★ ⚠ same residue
BARD1 p.Cys53Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Cys53fs Pathogenic/Likely 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

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-cys53tyr (accessed [today's date]).

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