Is BRCA1 p.Cys39Ter (c.117T>A) pathogenic?

BRCA1 p.Cys39Ter (c.117T>A) is classified Pathogenic in BRCA1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2021-03-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Cys39Ter (c.117T>A)?

BRCA1 p.Cys39Ter (c.117T>A) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Cys39Ter (c.117T>A) in the general population?

BRCA1 p.Cys39Ter (c.117T>A) is absent from gnomAD v4.1 (gnomAD).

BRCA1 p.Cys39Ter

c.117T>A · rs886040898 · VCV479243

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.52, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BRCA1
Protein: p.Cys39Ter
Coding: c.117T>A
MANE Select: NM_007294
dbSNP: rs886040898
Type: single nucleotide variant
Location: chr17:43115743 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

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

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 pancreatic cancer, susceptibility to, 4 hereditary breast carcinoma Fanconi anemia, complementation group S

Similar variants

BRCA1 p.Cys39Arg Pathogenic ★★★ same residue
BRCA1 p.Cys39Gly Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys39Phe Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys39Ser Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys39Trp Pathogenic ★★ same residue
BRCA1 p.Cys39Tyr Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys39_Asp40delinsTer Pathogenic ★★★ same residue
BRCA1 p.Cys39fs Pathogenic ★ same residue

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-cys39ter (accessed [today's date]).

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