Is BRCA1 p.Ser1379= (c.4137T>C) pathogenic?

BRCA1 p.Ser1379= (c.4137T>C) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-22). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ser1379= (c.4137T>C)?

BRCA1 p.Ser1379= (c.4137T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Ser1379= (c.4137T>C) in the general population?

BRCA1 p.Ser1379= (c.4137T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

BRCA1 p.Ser1379=

c.4137T>C · rs1057521866 · VCV384118

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -1.2, phastCons 0.99
Overall
CADD	6.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,586 alleles

Overall 6.2e-05% 1/1,612,956 alleles · very rare exomes 1/1,460,634 · genomes 0/152,322 · joint denominator

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: BRCA1
Protein: p.Ser1379=
Coding: c.4137T>C
MANE Select: NM_007294
dbSNP: rs1057521866
Type: single nucleotide variant
Location: chr17:43090992 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1379: a UniProt-annotated variant site (in fancs); the 'disordered' region

Full BRCA1 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

Similar variants

BRCA1 p.Ser1379Phe Uncertain significance ★ ⚠ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A Pathogenic ★★★ same condition
BRCA1 c.212+1G>T Pathogenic ★★★ same condition
BRCA1 c.212+3A>G Pathogenic ★★★ same condition
BRCA1 c.213-12A>G Pathogenic ★★★ same condition
BRCA1 c.213-15A>G 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/brca1-p-ser1379 (accessed [today's date]).

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