Is BRCA1 p.Arg1699= (c.5097G>T) pathogenic?

BRCA1 p.Arg1699= (c.5097G>T) is classified Likely benign in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Arg1699= (c.5097G>T)?

BRCA1 p.Arg1699= (c.5097G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Arg1699= (c.5097G>T) in the general population?

BRCA1 p.Arg1699= (c.5097G>T) is absent from gnomAD v4.1 (gnomAD).

BRCA1 p.Arg1699=

c.5097G>T · rs2051927969 · VCV1745302

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 1
Overall
CADD	8.548	PHRED · no single calibrated threshold — expert panels disagree

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.Arg1699=
Coding: c.5097G>T
MANE Select: NM_007294
dbSNP: rs2051927969
Type: single nucleotide variant
Location: chr17:43063929 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1699: the brct 1 domain; a UniProt-annotated variant site (in fancs); a UniProt-annotated variant site (in bc; pathogenic; strongly reduces affinity for a brip1 phosphopeptide; functionally impaired in vitro); a UniProt-annotated variant site (in bc, oc and fancs; impairs protein stability; functionally impaired in vitro)

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.Arg1699Gln Pathogenic ★★★ ⚠ same residue
BRCA1 p.Arg1699Trp Pathogenic ★★★ same residue
BRCA1 p.Arg1699Pro Uncertain significance ★★★ ⚠ same residue
BRCA1 p.Arg1699Leu 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
BRCA1 c.212+1G>T 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-arg1699 (accessed [today's date]).

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