Is CFD p.Gln44fs (c.132del) pathogenic?

CFD p.Gln44fs (c.132del) is classified Pathogenic in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). Very rare (popmax 0.00413%, afr).

How common is CFD p.Gln44fs (c.132del) in the general population?

CFD p.Gln44fs (c.132del) is very rare (popmax 0.00413%, afr) (gnomAD).

CFD p.Gln44fs

c.132del · rs1290545249 · VCV2900060

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00413%, afr)

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 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 1.5, phastCons 1
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00413% African / African-American · 3/72,660 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000504%

Overall 0.000968% 15/1,549,542 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00413%	24,220
European (non-Finnish)	0.00104%	96,463

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.Gln44fs
Coding: c.132del
MANE Select: NM_001928
dbSNP: rs1290545249
Type: Deletion
Location: chr19:860693 (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 44: the peptidase s1 domain; a β-strand

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

Similar variants

CFD p.Glu89fs Likely pathogenic ★ same type
CFD p.Val97fs Likely pathogenic ★ same type
CFD p.Arg140_Leu147del Uncertain significance ★ same type
CFD p.Glu219_Val222del Uncertain significance ★ same type
CFD p.Pro163fs Uncertain significance ★ same type

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-gln44fs (accessed [today's date]).

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