Is C3 p.Glu1040fs (c.3116dup) pathogenic?

C3 p.Glu1040fs (c.3116dup) is classified Pathogenic in C3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Associated with complement component 3 deficiency.

What condition is associated with C3 p.Glu1040fs (c.3116dup)?

C3 p.Glu1040fs (c.3116dup) is associated with complement component 3 deficiency (ClinVar).

How is Complement component 3 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

C3 p.Glu1040fs

c.3116dup · VCV4280175

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

complement component 3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -3.8

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

Variant & gene context

Gene: C3
Protein: p.Glu1040fs
Coding: c.3116dup
MANE Select: NM_000064
Type: Duplication
Location: chr19:6694468 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 1040: a disulfide bond

Full C3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Complement component 3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

C3 p.Glu1040Ala Uncertain significance ★ ⚠ same residue
C3 p.Asn103fs Pathogenic/Likely pathogenic ★★ same condition
C3 p.Leu125fs Pathogenic/Likely pathogenic ★★ same condition
C3 c.-3_-2dup Benign/Likely benign ★★ same condition
C3 p.Glu1040= Likely benign ★★ same residue
C3 p.Lys688fs Likely pathogenic ★ same condition
C3 p.Thr1272fs Likely pathogenic ★ same condition
C3 c.1003+1G>A Pathogenic/Likely 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/c3-p-glu1040fs (accessed [today's date]).

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