Is BARD1 p.Arg43His (c.128G>A) pathogenic?

BARD1 p.Arg43His (c.128G>A) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1928); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Arg43His (c.128G>A)?

BARD1 p.Arg43His (c.128G>A) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Arg43His (c.128G>A) in the general population?

BARD1 p.Arg43His (c.128G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARD1 p.Arg43His (c.128G>A)?

AlphaMissense predicts likely benign (score 0.1928) — an in-silico prediction, not a clinical call.

BARD1 p.Arg43His

c.128G>A · rs1060501305 · VCV628134

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1928 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1928	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg43His
Coding: c.128G>A
MANE Select: NM_000465
dbSNP: rs1060501305
Type: single nucleotide variant
Location: chr2:214809442 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 43: 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.Arg43Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Pro Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg43Ser 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-arg43his (accessed [today's date]).

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