Is BARD1 p.Ile573Arg (c.1718T>G) pathogenic?

BARD1 p.Ile573Arg (c.1718T>G) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.6163); Very rare (popmax 0.00223%, eas); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Ile573Arg (c.1718T>G)?

BARD1 p.Ile573Arg (c.1718T>G) is associated with BARD1-related cancer predisposition, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ile573Arg (c.1718T>G) in the general population?

BARD1 p.Ile573Arg (c.1718T>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BARD1 p.Ile573Arg (c.1718T>G)?

AlphaMissense predicts likely pathogenic (score 0.6163) — an in-silico prediction, not a clinical call.

BARD1 p.Ile573Arg

c.1718T>G · rs587780022 · VCV1917585

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BARD1-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.6163	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -13.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.56, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00223% East Asian · 1/44,852 alleles

Overall 0.000137% 2/1,461,740 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
European (non-Finnish)	8.47e-05%	1,179,952

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.Ile573Arg
Coding: c.1718T>G
MANE Select: NM_000465
dbSNP: rs587780022
Type: single nucleotide variant
Location: chr2:214745814 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 573: the brct 1 domain; a β-strand

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.Ile573Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile573Met Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile573Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Ile573= Likely benign ★★ same residue
BARD1 p.Ile573Lys Uncertain significance ★ ⚠ same residue
BARD1 p.Ile573Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BARD1 p.Ile573fs Pathogenic ★ same residue
BARD1 c.1314+1G>A Pathogenic/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-ile573arg (accessed [today's date]).

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