Is CFI p.Ter584Gln (c.1750T>C) pathogenic?

CFI p.Ter584Gln (c.1750T>C) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-11). Very rare (popmax 0.01%, amr); Associated with age related macular degeneration 13.

What condition is associated with CFI p.Ter584Gln (c.1750T>C)?

CFI p.Ter584Gln (c.1750T>C) is associated with age related macular degeneration 13, complement factor I deficiency, atypical hemolytic-uremic syndrome with I factor anomaly (ClinVar).

How common is CFI p.Ter584Gln (c.1750T>C) in the general population?

CFI p.Ter584Gln (c.1750T>C) is very rare (popmax 0.01%, amr) (gnomAD).

CFI p.Ter584Gln

c.1750T>C · rs184356649 · VCV2413947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

age related macular degeneration 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	15.01	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 0.01% Admixed American · 6/60,020 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000435% 7/1,610,092 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,003
African / African-American	0.00133%	74,962

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.Ter584Gln
Coding: c.1750T>C
MANE Select: NM_000204
dbSNP: rs184356649
Type: single nucleotide variant
Location: chr4:109740895 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB

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

Disease context

Also linked: complement factor I deficiency atypical hemolytic-uremic syndrome with I factor anomaly

Similar variants

CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same condition
CFI c.57+1G>C Likely pathogenic ★★ same condition
CFI c.658+1G>A Likely pathogenic ★★ same condition
CFI c.905-1G>C Likely pathogenic ★★ same condition
CFI p.Ala258Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ same condition
CFI p.Arg474Ter Pathogenic/Likely pathogenic ★★ same condition
CFI c.773-3C>T Uncertain significance ★★ 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/cfi-p-ter584gln (accessed [today's date]).

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