Is BARD1 p.Pro89= (c.267G>A) pathogenic?

BARD1 p.Pro89= (c.267G>A) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-04). Very rare (popmax 0.00502%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Pro89= (c.267G>A)?

BARD1 p.Pro89= (c.267G>A) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Pro89= (c.267G>A) in the general population?

BARD1 p.Pro89= (c.267G>A) is very rare (popmax 0.00502%, amr) (gnomAD).

BARD1 p.Pro89=

c.267G>A · rs756165637 · VCV184114

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -3.5, phastCons 0.36
Overall
CADD	8.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00502% Admixed American · 3/59,712 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00067%

Overall 0.0013% 19/1,460,674 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,904
African / African-American	0.00134%	74,350
European (non-Finnish)	0.00119%	84,226
South Asian	0.0011%	90,912

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.Pro89=
Coding: c.267G>A
MANE Select: NM_000465
dbSNP: rs756165637
Type: single nucleotide variant
Location: chr2:214792394 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 89: 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

BARD1 p.Pro89Arg Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro89Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro89Ala Uncertain significance ★ ⚠ same residue
BARD1 p.Pro89Gln Uncertain significance ★ ⚠ same residue
BARD1 p.Pro89fs Pathogenic ★★ same residue
BARD1 p.Pro89Thr Uncertain significance ★ ⚠ same residue
BARD1 c.1314+1G>A Pathogenic/Likely pathogenic ★★ same condition
BARD1 c.1314+1G>T 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-pro89 (accessed [today's date]).

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