Is CFD p.Glu89fs (c.265del) pathogenic?

CFD p.Glu89fs (c.265del) is classified Likely pathogenic in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-25). Very rare (popmax 0.00051%, nfe); Associated with CFD-related disorder.

What condition is associated with CFD p.Glu89fs (c.265del)?

CFD p.Glu89fs (c.265del) is associated with CFD-related disorder (ClinVar).

How common is CFD p.Glu89fs (c.265del) in the general population?

CFD p.Glu89fs (c.265del) is very rare (popmax 0.00051%, nfe) (gnomAD).

CFD p.Glu89fs

c.265del · VCV4939527

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Conditions

CFD-related disorder

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 2	GERP -2.2, phastCons 0.049

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,176,374 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000416% 6/1,443,396 alleles · very rare

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: CFD
Protein: p.Glu89fs
Coding: c.265del
MANE Select: NM_001928
Type: Deletion
Location: chr19:860912 (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 89: the peptidase s1 domain

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

Disease context

CFD-related disorder

Similar variants

CFD p.Val97fs Likely pathogenic ★ same condition
CFD p.Glu89Asp Uncertain significance ★ ⚠ same residue
CFD p.Glu89Gln Uncertain significance ★ ⚠ same residue
ELANE p.Ser126Leu Pathogenic ★★ ⚠ same condition
CFD p.Gln167His Uncertain significance ★★ ⚠ same condition
CFD c.212+1G>A Likely pathogenic ★ same condition
CFD c.55+1G>A Likely pathogenic ★ same condition
CFD c.-8G>A 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/cfd-p-glu89fs (accessed [today's date]).

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