Is BRCA1 p.Arg365= (c.1095A>G) pathogenic?

BRCA1 p.Arg365= (c.1095A>G) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-20). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Arg365= (c.1095A>G)?

BRCA1 p.Arg365= (c.1095A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Arg365= (c.1095A>G) in the general population?

BRCA1 p.Arg365= (c.1095A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

BRCA1 p.Arg365=

c.1095A>G · rs2154476392 · VCV2008407

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.066	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 0.32
Overall
CADD	1.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,062 alleles

Overall 6.84e-05% 1/1,461,800 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.Arg365=
Coding: c.1095A>G
MANE Select: NM_007294
dbSNP: rs2154476392
Type: single nucleotide variant
Location: chr17:43094436 (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

Similar variants

BRCA1 p.Arg365Ter Pathogenic ★★★ same residue
BRCA1 p.Arg365Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Arg365Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Arg365Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Arg365Thr Conflicting classifications of pathogenicity ★ ⚠ 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-arg365 (accessed [today's date]).

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