Is BARD1 p.Ser263= (c.789T>C) pathogenic?

BARD1 p.Ser263= (c.789T>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-11). Very rare (popmax 0.00135%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ser263= (c.789T>C)?

BARD1 p.Ser263= (c.789T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ser263= (c.789T>C) in the general population?

BARD1 p.Ser263= (c.789T>C) is very rare (popmax 0.00135%, afr) (gnomAD).

BARD1 p.Ser263=

c.789T>C · rs1345594874 · VCV481387

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

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 -0.26	GERP -4.5, phastCons 0.001
Overall
CADD	4.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/73,928 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000278% 4/1,440,928 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,928
European (non-Finnish)	0.000256%	390,637

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.Ser263=
Coding: c.789T>C
MANE Select: NM_000465
dbSNP: rs1345594874
Type: single nucleotide variant
Location: chr2:214781085 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

BARD1 p.Ser263Asn Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser263Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser263Arg Uncertain significance ★ same residue
BARD1 p.Ser263Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Ser263fs 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-ser263 (accessed [today's date]).

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