Is BARD1 p.Ile573Thr (c.1718T>C) pathogenic?

BARD1 p.Ile573Thr (c.1718T>C) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-04-15). AlphaMissense: likely benign (0.133); Ultra-rare (popmax 0.0164%, mid); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Ile573Thr (c.1718T>C)?

BARD1 p.Ile573Thr (c.1718T>C) is associated with BARD1-related cancer predisposition, hereditary neoplastic syndrome, familial ovarian cancer (ClinVar).

How common is BARD1 p.Ile573Thr (c.1718T>C) in the general population?

BARD1 p.Ile573Thr (c.1718T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BARD1 p.Ile573Thr (c.1718T>C)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

BARD1 p.Ile573Thr

c.1718T>C · rs587780022 · VCV127722

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BARD1-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.685	pathogenic-leaning
SaProt	LLR -7.97	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
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	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00254% 41/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00446%	22,432
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00271%	36,874
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,996

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.Ile573Thr
Coding: c.1718T>C
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 familial ovarian cancer hereditary breast carcinoma

Similar variants

BARD1 p.Ile573Arg Uncertain significance ★★ ⚠ same residue
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.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-ile573thr (accessed [today's date]).

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