Is CFI p.Arg187Ter (c.559C>T) pathogenic?

CFI p.Arg187Ter (c.559C>T) is classified Pathogenic/Likely pathogenic in CFI (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-04-06). Very rare (popmax 0.00935%, afr); Associated with CFI-related disorder.

What condition is associated with CFI p.Arg187Ter (c.559C>T)?

CFI p.Arg187Ter (c.559C>T) is associated with CFI-related disorder, complement factor I deficiency, atypical hemolytic-uremic syndrome with I factor anomaly (ClinVar).

How common is CFI p.Arg187Ter (c.559C>T) in the general population?

CFI p.Arg187Ter (c.559C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

CFI p.Arg187Ter

c.559C>T · rs368615806 · VCV631934

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

CFI-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.77, phastCons 1
Overall
CADD	36.0	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 0.00935% African / African-American · 7/74,846 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.0026% 42/1,613,470 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,692
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.00237%	42,131
East Asian	0.00223%	44,876
Admixed American	0.00167%	60,000
South Asian	0.0011%	91,062

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.Arg187Ter
Coding: c.559C>T
MANE Select: NM_000204
dbSNP: rs368615806
Type: single nucleotide variant
Location: chr4:109761616 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 187: a disulfide bond; the srcr domain

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 age related macular degeneration 13

Similar variants

CFI p.Arg187Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CFI p.Arg187Pro Uncertain significance ★ ⚠ same residue
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.Arg474Ter Pathogenic/Likely pathogenic ★★ 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-arg187ter (accessed [today's date]).

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