Is BRCA1 p.Ser889fs (c.2666_2667del) pathogenic?

BRCA1 p.Ser889fs (c.26662667del) is classified Pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-10). Associated with Fanconi anemia, complementation group S.

What condition is associated with BRCA1 p.Ser889fs (c.2666_2667del)?

BRCA1 p.Ser889fs (c.2666_2667del) is associated with Fanconi anemia, complementation group S (ClinVar).

BRCA1 p.Ser889fs

c.2666_2667del · VCV3778927

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Fanconi anemia, complementation group S

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -4.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BRCA1
Protein: p.Ser889fs
Coding: c.2666_2667del
MANE Select: NM_007294
Type: Microsatellite
Location: chr17:43092864 (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

Fanconi anemia, complementation group S — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA1 p.Ala1082_Met1083insTer Pathogenic ★★★ same condition
BRCA1 p.Gln1388_Ser1389insTer Pathogenic ★★★ same condition
BRCA1 p.Gly1077fs Pathogenic ★★★ same condition
BRCA1 p.Leu156_Ser157insTer Pathogenic ★★★ same condition
BRCA1 p.Lys800fs Pathogenic ★★★ same condition
BRCA1 p.Ser616del Benign ★★★ same condition
BRCA1 p.Val802fs Pathogenic ★★ same condition
BRCA1 c.4185+11TG[5] Benign/Likely benign ★★ 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-ser889fs (accessed [today's date]).

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