Is BARD1 p.Ala212= (c.636T>C) pathogenic?

BARD1 p.Ala212= (c.636T>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-22). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ala212= (c.636T>C)?

BARD1 p.Ala212= (c.636T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ala212= (c.636T>C) in the general population?

BARD1 p.Ala212= (c.636T>C) is absent from gnomAD v4.1 (gnomAD).

BARD1 p.Ala212=

c.636T>C · rs2106111263 · VCV2696432

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.32	GERP -2.1, phastCons 0.41
Overall
CADD	8.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BARD1
Protein: p.Ala212=
Coding: c.636T>C
MANE Select: NM_000465
dbSNP: rs2106111263
Type: single nucleotide variant
Location: chr2:214781238 (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 carcinoma

Similar variants

BARD1 p.Ala212Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Ala212Val Uncertain significance ★★ ⚠ same residue
BARD1 p.Ala212Ser Uncertain significance ★ ⚠ same residue
BARD1 p.Ala212Leu Uncertain significance ★ same residue
BARD1 p.Ala212Phe 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-ala212 (accessed [today's date]).

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