Is BARD1 p.Asp500Glu (c.1500T>G) pathogenic?

BARD1 p.Asp500Glu (c.1500T>G) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-16). AlphaMissense: likely pathogenic (0.8316); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Asp500Glu (c.1500T>G)?

BARD1 p.Asp500Glu (c.1500T>G) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Asp500Glu (c.1500T>G) in the general population?

BARD1 p.Asp500Glu (c.1500T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARD1 p.Asp500Glu (c.1500T>G)?

AlphaMissense predicts likely pathogenic (score 0.8316) — an in-silico prediction, not a clinical call.

BARD1 p.Asp500Glu

c.1500T>G · rs1694266892 · VCV1489516

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8316 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8316	likely pathogenic · top 10% in BARD1
REVEL	0.396	indeterminate
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -4.5
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	11.8	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

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.Asp500Glu
Coding: c.1500T>G
MANE Select: NM_000465
dbSNP: rs1694266892
Type: single nucleotide variant
Location: chr2:214767550 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 500: 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.Asp500Asn Uncertain significance ★★ ⚠ same residue
BARD1 p.Asp500His Uncertain significance ★★ ⚠ same residue
BARD1 p.Asp500Tyr Uncertain significance ★★ ⚠ same residue
BARD1 p.Asp500Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Asp500= Benign/Likely benign ★★ same residue
BARD1 p.Asp500Ala Uncertain significance ★ ⚠ same residue
BARD1 p.Asp500Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Asp500fs Pathogenic ★★ same residue

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-asp500glu (accessed [today's date]).

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