Is BARD1 p.Asp612Val (c.1835A>T) pathogenic?

BARD1 p.Asp612Val (c.1835A>T) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-07-29). AlphaMissense: likely benign (0.1323); Ultra-rare (popmax 0.0233%, amr); Associated with Hereditary cancer.

What condition is associated with BARD1 p.Asp612Val (c.1835A>T)?

BARD1 p.Asp612Val (c.1835A>T) is associated with Hereditary cancer, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Asp612Val (c.1835A>T) in the general population?

BARD1 p.Asp612Val (c.1835A>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about BARD1 p.Asp612Val (c.1835A>T)?

AlphaMissense predicts likely benign (score 0.1323) — an in-silico prediction, not a clinical call.

BARD1 p.Asp612Val

c.1835A>T · rs201140528 · VCV142336

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

AlphaMissense

likely benign

0.1323 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hereditary cancer

Computational evidence

Protein change
AlphaMissense	0.1323	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.65	acceptor gain · deltas
Pangolin	Δ0.56	gain · loss 0.30 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.5	GERP 0.84, phastCons 0.94
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	19.79	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 0.0233% Admixed American · 14/59,986 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0123% 199/1,613,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,285
European (non-Finnish)	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Finnishnot grpmax-eligible	0.00156%	64,022

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.Asp612Val
Coding: c.1835A>T
MANE Select: NM_000465
dbSNP: rs201140528
Type: single nucleotide variant
Location: chr2:214745135 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 612: the brct 1 domain; a β-strand

Full BARD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hereditary cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Asp612Asn Uncertain significance ★ ⚠ same residue
BARD1 p.Asp612Glu Uncertain significance ★ ⚠ same residue
BARD1 p.Asp612Gly Uncertain significance ★ ⚠ same residue
BARD1 p.Asp612= Likely benign ★ same residue
BARD1 p.Asp612Ter 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

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-asp612val (accessed [today's date]).

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