Is BARD1 p.Thr351= (c.1053G>C) pathogenic?

BARD1 p.Thr351= (c.1053G>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Common (popmax 23.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Thr351= (c.1053G>C)?

BARD1 p.Thr351= (c.1053G>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, hereditary breast carcinoma (ClinVar).

BARD1 p.Thr351=

Q: How common is BARD1 p.Thr351= (c.1053G>C) in the general population?

BARD1 p.Thr351= (c.1053G>C) is common (popmax 23.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1053G>C · rs2070096 · VCV142025

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Common

common (popmax 23.8%, sas) — 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 -6.7	GERP -4.2
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.8% South Asian · 21,709/91,078 alleles

Filtering AF 23.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.5%

Overall 21.4% 346,096/1,613,832 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	24.4%	4
South Asiangrpmax	23.8%	4
Admixed American	22.4%	4
European (non-Finnish)	22.1%	5
Remaining individualsnot grpmax-eligible	20.9%	5
Middle Eastern	20.6%	5
Amishnot grpmax-eligible	18.9%	5
East Asian	16.8%	6
African / African-American	16.4%	6
Finnishnot grpmax-eligible	13.3%	8

Ashkenazi Jewish 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.Thr351=
Coding: c.1053G>C
MANE Select: NM_000465
dbSNP: rs2070096
Type: single nucleotide variant
Location: chr2:214780821 (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.Thr351Ala Uncertain significance ★★ ⚠ same residue
BARD1 p.Thr351Met 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
BARD1 c.1396-2A>C 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-thr351 (accessed [today's date]).

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