Is BARD1 p.Arg565His (c.1694G>A) pathogenic?

BARD1 p.Arg565His (c.1694G>A) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 20 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.107); Rare (popmax 0.175%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Arg565His (c.1694G>A)?

BARD1 p.Arg565His (c.1694G>A) is associated with hereditary neoplastic syndrome, breast cancer, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Arg565His (c.1694G>A) in the general population?

BARD1 p.Arg565His (c.1694G>A) is rare (popmax 0.175%, sas) (gnomAD).

What do computational predictors say about BARD1 p.Arg565His (c.1694G>A)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

BARD1 p.Arg565His

c.1694G>A · rs146946984 · VCV127721

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 20 submitters

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.175%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.76	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 2.2	GERP 2.1, phastCons 0.91
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	21.3	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 0.175% South Asian · 159/91,078 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.144%

Overall 0.0211% 340/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.175%	573
Middle Eastern	0.149%	673
Ashkenazi Jewishnot grpmax-eligible	0.105%	955
Remaining individualsnot grpmax-eligible	0.048%	2,083
East Asian	0.00892%	11,214
European (non-Finnish)	0.00864%	11,568
Admixed American	0.005%	20,006
African / African-American	0.00267%	37,517

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.Arg565His
Coding: c.1694G>A
MANE Select: NM_000465
dbSNP: rs146946984
Type: single nucleotide variant
Location: chr2:214745838 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 565: the brct 1 domain

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: breast cancer hereditary breast carcinoma

Similar variants

BARD1 p.Arg565Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg565Leu Uncertain significance ★★ ⚠ same residue
BARD1 p.Arg565= Benign/Likely benign ★★ same residue
BARD1 p.Arg565Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Arg565Ser 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-arg565his (accessed [today's date]).

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