Is BARD1 p.His506= (c.1518T>C) pathogenic?

BARD1 p.His506= (c.1518T>C) is classified Benign in BARD1 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.His506= (c.1518T>C)?

BARD1 p.His506= (c.1518T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, hereditary breast carcinoma (ClinVar).

BARD1 p.His506=

Q: How common is BARD1 p.His506= (c.1518T>C) in the general population?

BARD1 p.His506= (c.1518T>C) is common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1518T>C · rs2070093 · VCV183704

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4.5
Overall
CADD	1.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.1% East Asian · 42,227/44,864 alleles

Filtering AF 93.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 93.1%

Overall 80.3% 1,294,591/1,612,710 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	94.1%	1
Finnishnot grpmax-eligible	89.3%	1
South Asian	84.1%	1
Ashkenazi Jewishnot grpmax-eligible	82.4%	1
European (non-Finnish)	80.4%	1
Admixed American	79.4%	1
Remaining individualsnot grpmax-eligible	78.9%	1
Amishnot grpmax-eligible	75.7%	1
Middle Eastern	75.6%	1
African / African-American	59.2%	2

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.His506=
Coding: c.1518T>C
MANE Select: NM_000465
dbSNP: rs2070093
Type: single nucleotide variant
Location: chr2:214767532 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary breast carcinoma

Similar variants

BARD1 p.His506Gln Uncertain significance ★★ ⚠ same residue
BARD1 p.His506Pro Uncertain significance ★ ⚠ same residue
BARD1 p.His506fs Pathogenic ★★ same residue
BARD1 p.His506_Val507delinsProMet Uncertain significance ★ same residue
BARD1 p.His506_Val507delinsTyrMet Uncertain significance ★ 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-his506 (accessed [today's date]).

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