Is BRCA1 p.Gln1811Ter (c.5431C>T) pathogenic?

BRCA1 p.Gln1811Ter (c.5431C>T) is classified Pathogenic in BRCA1 (ClinVar, Expert panel, 19 submitters; last evaluated 2016-10-18). Very rare (popmax 8.47e-05%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Gln1811Ter (c.5431C>T)?

BRCA1 p.Gln1811Ter (c.5431C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 1, urinary bladder cancer, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Gln1811Ter (c.5431C>T) in the general population?

BRCA1 p.Gln1811Ter (c.5431C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

BRCA1 p.Gln1811Ter

c.5431C>T · rs397509283 · VCV55577

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 19 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (22 of 23, 36 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
REVEL	0.39	indeterminate
Splicing
SpliceAI	Δ0.38	acceptor loss, 24 bp away · raw score · deltas
Pangolin	Δ0.52	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.3	GERP 0.49, phastCons 1
Overall
CADD	39.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,876 alleles · very rare

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.Gln1811Ter
Coding: c.5431C>T
MANE Select: NM_007294
dbSNP: rs397509283
Type: single nucleotide variant
Location: chr17:43047679 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1811: a UniProt-annotated variant site (in fancs); the brct 2 domain

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: urinary bladder cancer hereditary breast ovarian cancer syndrome pancreatic cancer, susceptibility to, 4 hereditary neoplastic syndrome hereditary breast carcinoma

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Gln1811Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
BRCA1 p.Gln1811Pro Likely pathogenic ★ ⚠ same residue
BRCA1 p.Gln1811His Uncertain significance ★ ⚠ same residue
BRCA1 p.Gln1811Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Gln1811fs Pathogenic/Likely pathogenic ★★ 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

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-gln1811ter (accessed [today's date]).

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