Is BARD1 p.Arg406Gln (c.1217G>A) pathogenic?

BARD1 p.Arg406Gln (c.1217G>A) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0861); Ultra-rare (popmax 0.0263%, sas); Associated with BARD1-related cancer predisposition.

What condition is associated with BARD1 p.Arg406Gln (c.1217G>A)?

BARD1 p.Arg406Gln (c.1217G>A) is associated with BARD1-related cancer predisposition, colon carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Arg406Gln (c.1217G>A) in the general population?

BARD1 p.Arg406Gln (c.1217G>A) is ultra-rare (popmax 0.0263%, sas) (gnomAD).

What do computational predictors say about BARD1 p.Arg406Gln (c.1217G>A)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

BARD1 p.Arg406Gln

c.1217G>A · rs587780014 · VCV127713

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BARD1-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -6.89	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 3.3	GERP 0.086, phastCons 0.88
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	16.51	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 0.0263% South Asian · 24/91,082 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00242% 39/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0263%	3,795
East Asian	0.0156%	6,413
Remaining individualsnot grpmax-eligible	0.0064%	15,620
African / African-American	0.00133%	74,918
European (non-Finnish)	0.000254%	393,326

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.Arg406Gln
Coding: c.1217G>A
MANE Select: NM_000465
dbSNP: rs587780014
Type: single nucleotide variant
Location: chr2:214780657 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB

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

Disease context

Also linked: colon carcinoma hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ same residue
BARD1 p.Arg406= Benign/Likely benign ★★ same residue
BARD1 p.Arg406Gly Conflicting classifications of pathogenicity ★ ⚠ 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-arg406gln (accessed [today's date]).

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