Is BRCA1 p.Ala1843= (c.5529A>C) pathogenic?

BRCA1 p.Ala1843= (c.5529A>C) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2020-10-08). Very rare (popmax 0.00535%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ala1843= (c.5529A>C)?

BRCA1 p.Ala1843= (c.5529A>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Ala1843= (c.5529A>C) in the general population?

BRCA1 p.Ala1843= (c.5529A>C) is very rare (popmax 0.00535%, afr) (gnomAD).

BRCA1 p.Ala1843=

c.5529A>C · rs1160863525 · VCV482890

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

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
Constraint at this position
Conservation	phyloP 3.3	GERP 0.68, phastCons 1
Overall
CADD	11.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,790 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/151,846 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.Ala1843=
Coding: c.5529A>C
MANE Select: NM_007294
dbSNP: rs1160863525
Type: single nucleotide variant
Location: chr17:43045741 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1843: 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

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.Ala1843Glu Likely pathogenic ★★★ ⚠ same residue
BRCA1 p.Ala1843Pro Likely pathogenic ★★ same residue
BRCA1 p.Ala1843Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1843fs 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-ala1843 (accessed [today's date]).

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