Is CFI p.Gly243Asp (c.728G>A) pathogenic?

CFI p.Gly243Asp (c.728G>A) is classified Pathogenic in CFI (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-03-01). AlphaMissense: likely pathogenic (0.6481); Very rare (popmax 0.00223%, eas); Associated with complement factor I deficiency.

What condition is associated with CFI p.Gly243Asp (c.728G>A)?

CFI p.Gly243Asp (c.728G>A) is associated with complement factor I deficiency (ClinVar).

How common is CFI p.Gly243Asp (c.728G>A) in the general population?

CFI p.Gly243Asp (c.728G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Immunodeficiency with factor I anomaly inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFI p.Gly243Asp (c.728G>A)?

AlphaMissense predicts likely pathogenic (score 0.6481) — an in-silico prediction, not a clinical call.

CFI p.Gly243Asp

c.728G>A · rs121964916 · VCV12124

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement factor I deficiency

Computational evidence

Protein change
AlphaMissense	0.6481	likely pathogenic ✓ concordant with ClinVar
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -12.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	24.2	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 0.00223% East Asian · 1/44,838 alleles

Overall 0.000657% 1/152,168 alleles · very rare

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.Gly243Asp
Coding: c.728G>A
MANE Select: NM_000204
dbSNP: rs121964916
Type: single nucleotide variant
Location: chr4:109760567 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 243: a disulfide bond; a UniProt-annotated variant site (in cfi deficiency); the ldl-receptor class a 1 domain; a β-strand

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

Disease context

complement factor I deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency with factor I anomaly (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

CFI p.Gly243= Likely benign ★★ same residue
CFI p.Gly243Arg Pathogenic ★ 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-gly243asp (accessed [today's date]).

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