Is BARD1 p.Ser401= (c.1203T>C) pathogenic?

BARD1 p.Ser401= (c.1203T>C) is classified Benign/Likely benign in BARD1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0374%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BARD1 p.Ser401= (c.1203T>C)?

BARD1 p.Ser401= (c.1203T>C) is associated with hereditary neoplastic syndrome, colon carcinoma, breast cancer (ClinVar).

How common is BARD1 p.Ser401= (c.1203T>C) in the general population?

BARD1 p.Ser401= (c.1203T>C) is ultra-rare (popmax 0.0374%, afr) (gnomAD).

BARD1 p.Ser401=

c.1203T>C · rs370553043 · VCV184869

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.59	GERP -0.54, phastCons 0.001
Overall
CADD	6.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0374% African / African-American · 28/74,920 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00669% 108/1,613,960 alleles · ultra-rare exomes 88/1,461,798 · genomes 20/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0374%	2,676
European (non-Finnish)	0.00602%	16,619
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Finnishnot grpmax-eligible	0.00469%	21,343
Admixed American	0.00333%	29,992
South Asian	0.0011%	91,082

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.Ser401=
Coding: c.1203T>C
MANE Select: NM_000465
dbSNP: rs370553043
Type: single nucleotide variant
Location: chr2:214780671 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.82 · 11 PDB
Residue 401: 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: colon carcinoma breast cancer lung cancer hereditary breast carcinoma

Similar variants

BARD1 p.Ser401Gly Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser401Thr Uncertain significance ★★ ⚠ same residue
BARD1 p.Ser401Arg Uncertain significance ★ ⚠ same residue
BARD1 p.Ser401Asn Uncertain significance ★ ⚠ same residue
BARD1 p.Ser401_Ser402insTer Pathogenic ★ 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-ser401 (accessed [today's date]).

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