Is CFI p.Cys550fs (c.1650_1651del) pathogenic?

CFI p.Cys550fs (c.16501651del) is classified Likely pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-27). Ultra-rare (popmax 0.0164%, mid).

How common is CFI p.Cys550fs (c.1650_1651del) in the general population?

CFI p.Cys550fs (c.1650_1651del) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CFI p.Cys550fs

c.1650_1651del · rs774728696 · VCV1163253

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	34.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.000254%	393,337

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.Cys550fs
Coding: c.1650_1651del
MANE Select: NM_000204
dbSNP: rs774728696
Type: Microsatellite
Location: chr4:109740994 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 550: a β-strand; 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.Cys550Tyr Likely pathogenic ★ same residue
CFI p.Cys550Arg Uncertain significance ★ ⚠ same residue
CFI p.Trp393fs Pathogenic ★★ same type
CFI c.57+5_57+8del Uncertain significance ★★ same type
CFI p.Arg480fs Pathogenic ★ same type
CFI p.Arg202del Uncertain significance ★ same type
CFI c.57+1GTAA[3] Likely benign ★ same type
CFI c.883+322TTGT[4] Benign ★ 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-cys550fs (accessed [today's date]).

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