Is BARD1 p.Ser16Phe (c.47C>T) pathogenic?

BARD1 p.Ser16Phe (c.47C>T) is classified Uncertain significance in BARD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.3453); Very rare (popmax 0.00171%, amr); Associated with hereditary breast carcinoma.

What condition is associated with BARD1 p.Ser16Phe (c.47C>T)?

BARD1 p.Ser16Phe (c.47C>T) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is BARD1 p.Ser16Phe (c.47C>T) in the general population?

BARD1 p.Ser16Phe (c.47C>T) is very rare (popmax 0.00171%, amr) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BARD1 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts ambiguous (score 0.3453) — an in-silico prediction, not a clinical call.

BARD1 p.Ser16Phe

c.47C>T · rs1326565823 · VCV825186

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3453 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.3453	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -8.55	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 0.11, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 81 kb · p 0.077 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,548 alleles

Overall 0.000126% 2/1,592,230 alleles · very rare exomes 1/1,440,016 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,548
South Asian	0.00112%	89,248

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.Ser16Phe
Coding: c.47C>T
MANE Select: NM_000465
dbSNP: rs1326565823
Type: single nucleotide variant
Location: chr2:214809523 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 16: the 'disordered' region

Full BARD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BARD1 p.Ser16Cys Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser16Tyr Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser16Ala Uncertain significance ★ ⚠ same residue
BARD1 p.Ser16= 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

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-ser16phe (accessed [today's date]).

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