Is BARD1 p.Ser397Pro (c.1188_1189delinsAC) pathogenic?

BARD1 p.Ser397Pro (c.11881189delinsAC) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-10). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ser397Pro (c.1188_1189delinsAC)?

BARD1 p.Ser397Pro (c.1188_1189delinsAC) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ser397Pro (c.1188_1189delinsAC) in the general population?

BARD1 p.Ser397Pro (c.1188_1189delinsAC) is no gnomAD frequency available for this variant (gnomAD).

BARD1 p.Ser397Pro

c.1188_1189delinsAC · rs1694952147 · VCV1045969

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.55	GERP -3.9, phastCons 0.002
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BARD1
Protein: p.Ser397Pro
Coding: c.1188_1189delinsAC
MANE Select: NM_000465
dbSNP: rs1694952147
Type: Indel
Location: chr2:214780685 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 397: 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: hereditary breast carcinoma

Similar variants

BARD1 p.Ser397Ala Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser397Tyr Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser397fs Pathogenic ★ same residue
BARD1 p.Ser397Cys Uncertain significance ★ ⚠ same residue
BARD1 p.Ser397Phe Uncertain significance ★ ⚠ same residue
BARD1 p.Ser397= Likely benign ★ same residue
BARD1 p.Ala25fs Pathogenic ★★ same condition
BARD1 p.Arg378fs 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-ser397pro (accessed [today's date]).

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