Is BRCA1 p.Arg1835Ter (c.5503C>T) pathogenic?

BRCA1 p.Arg1835Ter (c.5503C>T) is classified Pathogenic in BRCA1 (ClinVar, Expert panel, 58 submitters; last evaluated 2016-04-22). Very rare (popmax 0.00329%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Arg1835Ter (c.5503C>T)?

BRCA1 p.Arg1835Ter (c.5503C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 1, gastric cancer, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Arg1835Ter (c.5503C>T) in the general population?

BRCA1 p.Arg1835Ter (c.5503C>T) is very rare (popmax 0.00329%, sas) (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.Arg1835Ter

c.5503C>T · rs41293465 · VCV55601

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 58 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

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	escapes	premature termination codon in the last exon (23 of 23) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.8	GERP -1.8, 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

Grpmax group 0.00329% South Asian · 3/91,068 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00137% 20/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,356
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00136%	73,751

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.Arg1835Ter
Coding: c.5503C>T
MANE Select: NM_007294
dbSNP: rs41293465
Type: single nucleotide variant
Location: chr17:43045767 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1835: a UniProt-annotated variant site (in fancs); the brct 2 domain; an α-helix

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: gastric cancer hereditary breast ovarian cancer syndrome breast carcinoma breast cancer lung cancer pancreatic cancer, susceptibility to, 4 hereditary neoplastic syndrome hereditary breast carcinoma ovarian neoplasm breast neoplasm Fanconi anemia, complementation group S

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Arg1835Pro Uncertain significance ★★ ⚠ same residue
BRCA1 p.Arg1835Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Arg1835Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Arg1835= Likely benign ★ same residue
BRCA1 p.Arg1835fs 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-arg1835ter (accessed [today's date]).

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