Is BRCA1 p.Lys993= (c.2979A>G) pathogenic?

BRCA1 p.Lys993= (c.2979A>G) is classified Likely benign in BRCA1 (ClinVar, Expert panel, 11 submitters; last evaluated 2017-06-29). Ultra-rare (popmax 0.0373%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Lys993= (c.2979A>G)?

BRCA1 p.Lys993= (c.2979A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA1 p.Lys993= (c.2979A>G) in the general population?

BRCA1 p.Lys993= (c.2979A>G) is ultra-rare (popmax 0.0373%, 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.Lys993=

c.2979A>G · rs772854836 · VCV183786

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -4.5
Overall
CADD	1.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% South Asian · 34/91,074 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.00253% 37/1,461,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0373%	2,679
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	8.47e-05%	1,179,988

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.Lys993=
Coding: c.2979A>G
MANE Select: NM_007294
dbSNP: rs772854836
Type: single nucleotide variant
Location: chr17:43092552 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 993: a UniProt-annotated variant site (in fancs)

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: hereditary breast ovarian cancer syndrome breast cancer hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Lys993Glu Uncertain significance ★★ ⚠ same residue
BRCA1 p.Lys993Ter Pathogenic ★ same residue
BRCA1 p.Lys993_Cys994insTer Pathogenic ★★★ same residue
BRCA1 p.Lys993fs 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-lys993 (accessed [today's date]).

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