Is CFI p.Val481= (c.1443C>T) pathogenic?

CFI p.Val481= (c.1443C>T) is classified Benign/Likely benign in CFI (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.701%, afr); Associated with atypical hemolytic-uremic syndrome with I factor anomaly.

What condition is associated with CFI p.Val481= (c.1443C>T)?

CFI p.Val481= (c.1443C>T) is associated with atypical hemolytic-uremic syndrome with I factor anomaly, complement factor I deficiency, age related macular degeneration 13 (ClinVar).

How common is CFI p.Val481= (c.1443C>T) in the general population?

CFI p.Val481= (c.1443C>T) is rare (popmax 0.701%, afr) (gnomAD).

CFI p.Val481=

c.1443C>T · rs114091883 · VCV347150

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.701%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.41, phastCons 1
Overall
CADD	1.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.701% African / African-American · 525/74,896 alleles

Filtering AF 0.651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.632%

Overall 0.0348% 559/1,607,818 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.701%	143
Remaining individualsnot grpmax-eligible	0.0273%	3,666
Admixed American	0.02%	4,999
Middle Eastern	0.0165%	6,058
South Asian	0.0011%	90,956
European (non-Finnish)	0.000255%	391,463

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.Val481=
Coding: c.1443C>T
MANE Select: NM_000204
dbSNP: rs114091883
Type: single nucleotide variant
Location: chr4:109742582 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 481: a disulfide bond; the peptidase s1 domain

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 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
CFI c.773-3C>T Uncertain significance ★★ 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-val481 (accessed [today's date]).

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