Is CFI p.Asn428fs (c.1283del) pathogenic?

CFI p.Asn428fs (c.1283del) is classified Pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). Very rare (popmax 0.000169%, nfe).

How common is CFI p.Asn428fs (c.1283del) in the general population?

CFI p.Asn428fs (c.1283del) is very rare (popmax 0.000169%, nfe) (gnomAD).

CFI p.Asn428fs

c.1283del · rs778466816 · VCV2829643

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 11 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -3.5, phastCons 0.005

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)grpmax	0.000169%	590,012

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFI
Protein: p.Asn428fs
Coding: c.1283del
MANE Select: NM_000204
dbSNP: rs778466816
Type: Deletion
Location: chr4:109746368 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 428: a disulfide bond; the peptidase s1 domain

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

Similar variants

CFI p.Asn428Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CFI p.Asn549fs Likely pathogenic ★★ same type
CFI p.Glu434fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Gly263fs Pathogenic ★★ same type
CFI p.Leu484fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Lys89fs Pathogenic ★★ same type
CFI p.Met138fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Ala294del 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/cfi-p-asn428fs (accessed [today's date]).

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