Is BARD1 p.Pro246= (c.738A>G) pathogenic?

BARD1 p.Pro246= (c.738A>G) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0169%, nfe); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Pro246= (c.738A>G)?

BARD1 p.Pro246= (c.738A>G) is associated with BARD1-related cancer predisposition, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Pro246= (c.738A>G) in the general population?

BARD1 p.Pro246= (c.738A>G) is ultra-rare (popmax 0.0169%, nfe) (gnomAD).

BARD1 p.Pro246=

c.738A>G · rs587780859 · VCV136498

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, nfe)

Conditions

BARD1-related cancer predisposition

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 -1.6	GERP -2.8
Overall
CADD	3.536	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% European (non-Finnish) · 197/1,164,894 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0128% 201/1,574,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0169%	5,913
Remaining individualsnot grpmax-eligible	0.0066%	15,156

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.Pro246=
Coding: c.738A>G
MANE Select: NM_000465
dbSNP: rs587780859
Type: single nucleotide variant
Location: chr2:214781136 (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

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Pro246Gln Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro246Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro246Ser Uncertain significance ★★ ⚠ same residue
BARD1 p.Pro246Ala Uncertain significance ★ ⚠ same residue
BARD1 p.Pro246Arg Uncertain significance ★ ⚠ same residue
BARD1 p.Pro246Thr 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

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-pro246 (accessed [today's date]).

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