Is CFI p.Arg480fs (c.1440_1441del) pathogenic?

CFI p.Arg480fs (c.14401441del) is classified Pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). Very rare (popmax 0.0022%, sas).

How common is CFI p.Arg480fs (c.1440_1441del) in the general population?

CFI p.Arg480fs (c.1440_1441del) is very rare (popmax 0.0022%, sas) (gnomAD).

CFI p.Arg480fs

c.1440_1441del · rs1283565272 · VCV2022339

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,958 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000206% 3/1,455,254 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,479
Admixed American	0.00167%	59,976

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.Arg480fs
Coding: c.1440_1441del
MANE Select: NM_000204
dbSNP: rs1283565272
Type: Microsatellite
Location: chr4:109742584 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 480: 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.Trp393fs Pathogenic ★★ same type
CFI c.57+5_57+8del Uncertain significance ★★ same type
CFI p.Cys550fs Likely 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-arg480fs (accessed [today's date]).

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