Is BARD1 p.Arg155Ter (c.463A>T) pathogenic?

BARD1 p.Arg155Ter (c.463A>T) is classified Pathogenic in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Arg155Ter (c.463A>T)?

BARD1 p.Arg155Ter (c.463A>T) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Arg155Ter (c.463A>T) in the general population?

BARD1 p.Arg155Ter (c.463A>T) is absent from gnomAD v4.1 (gnomAD).

BARD1 p.Arg155Ter

c.463A>T · rs1553622669 · VCV460752

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP -0.36, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BARD1
Protein: p.Arg155Ter
Coding: c.463A>T
MANE Select: NM_000465
dbSNP: rs1553622669
Type: single nucleotide variant
Location: chr2:214781411 (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.Arg155Lys Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg155= Conflicting classifications of pathogenicity ★ same residue
BARD1 p.Arg155Ile Uncertain significance ★ ⚠ same residue
BARD1 p.Arg155Thr Uncertain significance ★ ⚠ same residue
BARD1 p.Arg155_Val157del Uncertain significance ★ 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-arg155ter (accessed [today's date]).

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