Is CFI p.Glu190Asp (c.570G>T) pathogenic?

CFI p.Glu190Asp (c.570G>T) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-16). AlphaMissense: likely pathogenic (0.8949); Ultra-rare (popmax 0.025%, amr); Associated with CFI-related disorder.

What condition is associated with CFI p.Glu190Asp (c.570G>T)?

CFI p.Glu190Asp (c.570G>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.Glu190Asp (c.570G>T) in the general population?

CFI p.Glu190Asp (c.570G>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about CFI p.Glu190Asp (c.570G>T)?

AlphaMissense predicts likely pathogenic (score 0.8949) — an in-silico prediction, not a clinical call.

CFI p.Glu190Asp

c.570G>T · rs200086211 · VCV1359466

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.8949	likely pathogenic
REVEL	0.487	indeterminate
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -0.22, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/60,028 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00192% 31/1,613,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,002
Remaining individualsnot grpmax-eligible	0.024%	4,167
African / African-American	0.00133%	75,036

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.Glu190Asp
Coding: c.570G>T
MANE Select: NM_000204
dbSNP: rs200086211
Type: single nucleotide variant
Location: chr4:109761605 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 190: 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.Glu190Ala Uncertain significance ★ ⚠ same residue
CFI p.Glu190Gln 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.Arg187Ter 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-glu190asp (accessed [today's date]).

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