Is BRCA1 p.Ser643fs (c.1929_1930delinsA) pathogenic?

BRCA1 p.Ser643fs (c.19291930delinsA) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-05-20). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ser643fs (c.1929_1930delinsA)?

BRCA1 p.Ser643fs (c.1929_1930delinsA) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Ser643fs (c.1929_1930delinsA) in the general population?

BRCA1 p.Ser643fs (c.1929_1930delinsA) is absent from gnomAD (gnomAD).

BRCA1 p.Ser643fs

c.1929_1930delinsA · rs886039982 · VCV480996

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 5.3	GERP 1.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA1
Protein: p.Ser643fs
Coding: c.1929_1930delinsA
MANE Select: NM_007294
dbSNP: rs886039982
Type: Indel
Location: chr17:43093601 (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 breast-ovarian cancer, familial, susceptibility to, 1

Similar variants

BRCA1 p.Ser643Gly Benign ★★★ ⚠ same residue
BRCA1 p.Ser643Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ser643Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ser643= Likely benign ★ same residue
BRCA1 c.4185+2_4185+22delinsA Pathogenic ★★★ same condition
BRCA1 c.5331_5332+1delinsCAACAT Pathogenic ★★★ same condition
BRCA1 p.Ala1039fs Pathogenic ★★★ same condition
BRCA1 p.Ala521_Asp522delinsTer 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-ser643fs (accessed [today's date]).

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