Is CFI p.Ala384Thr (c.1150G>A) pathogenic?

CFI p.Ala384Thr (c.1150G>A) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-15). AlphaMissense: likely benign (0.0971); Ultra-rare (popmax 0.0491%, amr); Associated with age related macular degeneration 13.

What condition is associated with CFI p.Ala384Thr (c.1150G>A)?

CFI p.Ala384Thr (c.1150G>A) is associated with age related macular degeneration 13, complement factor I deficiency, atypical hemolytic-uremic syndrome with I factor anomaly (ClinVar).

How common is CFI p.Ala384Thr (c.1150G>A) in the general population?

CFI p.Ala384Thr (c.1150G>A) is ultra-rare (popmax 0.0491%, amr) (gnomAD).

What do computational predictors say about CFI p.Ala384Thr (c.1150G>A)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

CFI p.Ala384Thr

c.1150G>A · rs762315947 · VCV1481445

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 13

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -2.4
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	6.021	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0491% Admixed American · 28/56,976 alleles

Filtering AF 0.0348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0301%

Overall 0.00207% 33/1,594,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0491%	2,035
European (non-Finnish)	0.000427%	234,367

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.Ala384Thr
Coding: c.1150G>A
MANE Select: NM_000204
dbSNP: rs762315947
Type: single nucleotide variant
Location: chr4:109746501 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 384: a disulfide bond; the peptidase s1 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 atypical hemolytic-uremic syndrome

Similar variants

CFI p.Ala384= Likely benign ★ 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-ala384thr (accessed [today's date]).

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