Is BARD1 p.Asp710Val (c.2129A>T) pathogenic?

BARD1 p.Asp710Val (c.2129A>T) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-02). AlphaMissense: likely pathogenic (0.8457); Very rare (popmax 0.00297%, nfe); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Asp710Val (c.2129A>T)?

BARD1 p.Asp710Val (c.2129A>T) is associated with BARD1-related cancer predisposition, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Asp710Val (c.2129A>T) in the general population?

BARD1 p.Asp710Val (c.2129A>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about BARD1 p.Asp710Val (c.2129A>T)?

AlphaMissense predicts likely pathogenic (score 0.8457) — an in-silico prediction, not a clinical call.

BARD1 p.Asp710Val

c.2129A>T · rs150121935 · VCV142456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.8457 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BARD1-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.8457	likely pathogenic · top 10% in BARD1
REVEL	0.478	indeterminate
SaProt	LLR -8.93	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	29.8	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

Grpmax group 0.00297% European (non-Finnish) · 35/1,180,034 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00229% 37/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,715
African / African-American	0.00267%	37,467

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.Asp710Val
Coding: c.2129A>T
MANE Select: NM_000465
dbSNP: rs150121935
Type: single nucleotide variant
Location: chr2:214728881 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 710: the brct 2 domain; an α-helix

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.Asp710= Benign/Likely benign ★★ same residue
BARD1 p.Asp710fs Pathogenic ★ 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
BARD1 c.1396-2A>C 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-asp710val (accessed [today's date]).

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