Is CFI p.Cys54Trp (c.162C>G) pathogenic?

CFI p.Cys54Trp (c.162C>G) is classified Conflicting classifications of pathogenicity in CFI (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9741); Absent from gnomAD v4.1; Associated with complement factor I deficiency.

What condition is associated with CFI p.Cys54Trp (c.162C>G)?

CFI p.Cys54Trp (c.162C>G) is associated with complement factor I deficiency (ClinVar).

How common is CFI p.Cys54Trp (c.162C>G) in the general population?

CFI p.Cys54Trp (c.162C>G) is absent from gnomAD v4.1 (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.Cys54Trp (c.162C>G)?

AlphaMissense predicts likely pathogenic (score 0.9741) — an in-silico prediction, not a clinical call.

CFI p.Cys54Trp

c.162C>G · rs1553915717 · VCV560185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

complement factor I deficiency

Computational evidence

Protein change
AlphaMissense	0.9741	likely pathogenic · top 7% in CFI
REVEL	0.61	indeterminate
SaProt	LLR -12.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.1, phastCons 0.9
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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFI
Protein: p.Cys54Trp
Coding: c.162C>G
MANE Select: NM_000204
dbSNP: rs1553915717
Type: single nucleotide variant
Location: chr4:109766720 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 54: a disulfide bond; 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.Cys54Tyr 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
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-cys54trp (accessed [today's date]).

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