Is CFI p.Met138fs (c.413del) pathogenic?

CFI p.Met138fs (c.413del) is classified Pathogenic/Likely pathogenic in CFI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). Associated with atypical hemolytic-uremic syndrome with I factor anomaly.

What condition is associated with CFI p.Met138fs (c.413del)?

CFI p.Met138fs (c.413del) is associated with atypical hemolytic-uremic syndrome with I factor anomaly, complement factor I deficiency, age related macular degeneration 13 (ClinVar).

CFI p.Met138fs

c.413del · VCV3589772

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

atypical hemolytic-uremic syndrome with I factor anomaly

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP 0.92, phastCons 0.25

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

Variant & gene context

Gene: CFI
Protein: p.Met138fs
Coding: c.413del
MANE Select: NM_000204
Type: Deletion
Location: chr4:109764606 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 138: a disulfide bond; the srcr domain; a β-strand

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

Disease context

atypical hemolytic-uremic syndrome with I factor anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: complement factor I deficiency age related macular degeneration 13

Similar variants

CFI p.Glu434fs Pathogenic/Likely pathogenic ★★ same condition
CFI p.Leu484fs Pathogenic/Likely pathogenic ★★ same condition
CFI p.Lys89fs Pathogenic ★★ same condition
CFI p.Asp27fs Pathogenic ★ same condition
CFI p.Met138Val Likely pathogenic ★ ⚠ same residue
CFI p.Met138Ile Uncertain significance ★ ⚠ same residue
CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same condition
CFI c.57+1G>C 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-met138fs (accessed [today's date]).

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