Is BARD1 p.Asp532Asn (c.1594G>A) pathogenic?

BARD1 p.Asp532Asn (c.1594G>A) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2431); Very rare (popmax 0.00446%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Asp532Asn (c.1594G>A)?

BARD1 p.Asp532Asn (c.1594G>A) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Asp532Asn (c.1594G>A) in the general population?

BARD1 p.Asp532Asn (c.1594G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BARD1 p.Asp532Asn (c.1594G>A)?

AlphaMissense predicts likely benign (score 0.2431) — an in-silico prediction, not a clinical call.

BARD1 p.Asp532Asn

c.1594G>A · rs757281184 · VCV185716

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2431	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.00446% East Asian · 2/44,816 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00103% 15/1,461,380 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,408
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,068
European (non-Finnish)	0.000932%	107,247

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.Asp532Asn
Coding: c.1594G>A
MANE Select: NM_000465
dbSNP: rs757281184
Type: single nucleotide variant
Location: chr2:214752530 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 532: an α-helix

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.Asp532Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Asp532= Likely benign ★★ same residue
BARD1 p.Asp532His 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
BARD1 c.1396-1G>C Likely pathogenic ★★ same condition
BARD1 c.1396-1G>T 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-asp532asn (accessed [today's date]).

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