Is BARD1 p.His606= (c.1818T>C) pathogenic?

BARD1 p.His606= (c.1818T>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-28). Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.His606= (c.1818T>C)?

BARD1 p.His606= (c.1818T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.His606= (c.1818T>C) in the general population?

BARD1 p.His606= (c.1818T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

BARD1 p.His606=

c.1818T>C · rs199590147 · VCV184356

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.036	GERP -3.4, phastCons 0.013
Overall
CADD	3.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000806% 13/1,613,420 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	0.00102%	98,292

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.His606=
Coding: c.1818T>C
MANE Select: NM_000465
dbSNP: rs199590147
Type: single nucleotide variant
Location: chr2:214745152 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 606: the brct 1 domain; a β-strand

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.His606Arg Uncertain significance ★★ ⚠ same residue
BARD1 p.His606Gln Uncertain significance ★★ ⚠ same residue
BARD1 p.His606Pro Uncertain significance ★★ ⚠ same residue
BARD1 p.His606Tyr Uncertain significance ★★ ⚠ same residue
BARD1 p.His606Asn Uncertain significance ★ ⚠ same residue
BARD1 p.His606Leu Uncertain significance ★ ⚠ same residue
BARD1 p.His606fs Pathogenic ★★ same residue
BARD1 c.1314+1G>A Pathogenic/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-his606 (accessed [today's date]).

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