Is BARD1 p.His556Arg (c.1667A>G) pathogenic?

BARD1 p.His556Arg (c.1667A>G) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-28). AlphaMissense: likely benign (0.0615); Absent from gnomAD v4.1.

How common is BARD1 p.His556Arg (c.1667A>G) in the general population?

BARD1 p.His556Arg (c.1667A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARD1 p.His556Arg (c.1667A>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

BARD1 p.His556Arg

c.1667A>G · rs2106038583 · VCV2682137

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.53	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 -0.087	GERP -3.9, phastCons 0.11
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	8.759	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.His556Arg
Coding: c.1667A>G
MANE Select: NM_000465
dbSNP: rs2106038583
Type: single nucleotide variant
Location: chr2:214752457 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 556: the 'flexible linker' region

Full BARD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BARD1 p.His556Gln Uncertain significance ★★ ⚠ same residue
BARD1 p.His556Tyr Uncertain significance ★★ ⚠ same residue
BARD1 p.His556= Benign/Likely benign ★★ same residue
BARD1 p.His556fs Pathogenic ★ same residue
BARD1 c.1314+1G>A Pathogenic/Likely pathogenic ★★ same type
BARD1 c.1314+1G>T Likely pathogenic ★★ same type
BARD1 c.1396-1G>A Likely pathogenic ★★ same type
BARD1 c.1396-1G>C Likely pathogenic ★★ same type

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-his556arg (accessed [today's date]).

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