Is CFD p.Leu94fs (c.278_279dup) pathogenic?

CFD p.Leu94fs (c.278279dup) is classified Likely pathogenic in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). Associated with recurrent Neisseria infections due to factor D deficiency.

What condition is associated with CFD p.Leu94fs (c.278_279dup)?

CFD p.Leu94fs (c.278_279dup) is associated with recurrent Neisseria infections due to factor D deficiency (ClinVar).

CFD p.Leu94fs

Q: How is Recurrent Neisseria infections due to factor D deficiency inherited?

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

c.278_279dup · VCV3779512

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

recurrent Neisseria infections due to factor D 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 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1

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

Variant & gene context

Gene: CFD
Protein: p.Leu94fs
Coding: c.278_279dup
MANE Select: NM_001928
Type: Microsatellite
Location: chr19:860923 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.19 · 40 PDB
Residue 94: the peptidase s1 domain; a β-strand

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

Disease context

recurrent Neisseria infections due to factor D deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recurrent Neisseria infections due to factor D deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

CFD p.Leu94Gln Uncertain significance ★ ⚠ same residue
CFD c.212+2T>G Likely pathogenic ★★ same condition
CFD c.56-1G>C Likely pathogenic ★★ same condition
CFD p.Tyr95Ter Pathogenic ★★ same condition
CFD c.213-1G>C Likely pathogenic ★ same condition
CFD p.Ser42Ter Pathogenic ★ same condition
CFD p.Gly216Ser Uncertain significance ★ ⚠ same condition
CFD p.Gly52Asp Uncertain significance ★ ⚠ 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/cfd-p-leu94fs (accessed [today's date]).

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