Is BARD1 p.Gln11His (c.33G>T) pathogenic?

BARD1 p.Gln11His (c.33G>T) is classified Conflicting classifications of pathogenicity in BARD1 (ClinVar, Conflicting submitters, 26 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1802); Rare (popmax 0.256%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Gln11His (c.33G>T)?

BARD1 p.Gln11His (c.33G>T) is associated with hereditary neoplastic syndrome, breast cancer, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Gln11His (c.33G>T) in the general population?

BARD1 p.Gln11His (c.33G>T) is rare (popmax 0.256%, amr) (gnomAD).

What do computational predictors say about BARD1 p.Gln11His (c.33G>T)?

AlphaMissense predicts likely benign (score 0.1802) — an in-silico prediction, not a clinical call.

BARD1 p.Gln11His

c.33G>T · rs143914387 · VCV127737

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 26 submitters

AlphaMissense

likely benign

0.1802 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.256%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1802	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.83	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 -0.12	GERP -1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	14.91	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 0.256% Admixed American · 146/57,008 alleles

Filtering AF 0.222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.209%

Overall 0.157% 2,481/1,577,884 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.352%	284
Admixed Americangrpmax	0.256%	390
Amishnot grpmax-eligible	0.219%	456
European (non-Finnish)	0.168%	594
Remaining individualsnot grpmax-eligible	0.159%	630
Middle Eastern	0.134%	747
Ashkenazi Jewishnot grpmax-eligible	0.0827%	1,210
South Asian	0.0408%	2,451
African / African-American	0.0216%	4,638
East Asian	0.00232%	43,040

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln11His
Coding: c.33G>T
MANE Select: NM_000465
dbSNP: rs143914387
Type: single nucleotide variant
Location: chr2:214809537 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 11: the 'disordered' region

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: breast cancer hereditary breast carcinoma

Similar variants

BARD1 p.Gln11Leu Uncertain significance ★ ⚠ same residue
BARD1 p.Gln11Pro Uncertain significance ★ ⚠ same residue
BARD1 p.Gln11_Arg15del Uncertain significance ★★ same residue
BARD1 p.Gln11_Arg15dup Uncertain significance ★★ same residue
BARD1 p.Gln11fs 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-gln11his (accessed [today's date]).

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