Is BARD1 p.Ser409Pro (c.1225T>C) pathogenic?

BARD1 p.Ser409Pro (c.1225T>C) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-23). AlphaMissense: likely benign (0.0771); Absent from gnomAD v4.1; Associated with BARD1-related disorder.

What condition is associated with BARD1 p.Ser409Pro (c.1225T>C)?

BARD1 p.Ser409Pro (c.1225T>C) is associated with BARD1-related disorder, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BARD1 p.Ser409Pro (c.1225T>C) in the general population?

BARD1 p.Ser409Pro (c.1225T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARD1 p.Ser409Pro (c.1225T>C)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

BARD1 p.Ser409Pro

c.1225T>C · rs2106108006 · VCV1485151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BARD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.36	GERP -0.7
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	11.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser409Pro
Coding: c.1225T>C
MANE Select: NM_000465
dbSNP: rs2106108006
Type: single nucleotide variant
Location: chr2:214780649 (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

BARD1-related disorder

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BARD1 p.Ser409Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser409Phe Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser409= Likely benign ★ 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

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-ser409pro (accessed [today's date]).

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