Is CFI p.Ser470= (c.1410T>C) pathogenic?

CFI p.Ser470= (c.1410T>C) is classified Benign/Likely benign in CFI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Rare (popmax 0.316%, eas); Associated with atypical hemolytic-uremic syndrome with I factor anomaly.

What condition is associated with CFI p.Ser470= (c.1410T>C)?

CFI p.Ser470= (c.1410T>C) is associated with atypical hemolytic-uremic syndrome with I factor anomaly (ClinVar).

How common is CFI p.Ser470= (c.1410T>C) in the general population?

CFI p.Ser470= (c.1410T>C) is rare (popmax 0.316%, eas) (gnomAD).

CFI p.Ser470=

c.1410T>C · rs200068862 · VCV347154

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.316%, eas)

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 1.3	GERP -2.2, phastCons 1
Overall
CADD	7.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% East Asian · 142/44,890 alleles

Filtering AF 0.274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.00997% 161/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.316%	316
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00878%	11,385
Admixed American	0.00167%	60,018

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.Ser470=
Coding: c.1410T>C
MANE Select: NM_000204
dbSNP: rs200068862
Type: single nucleotide variant
Location: chr4:109746241 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 470: a β-strand; 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

Similar variants

CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same condition
CFI c.57+1G>C 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
CFI c.940+6C>A 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-ser470 (accessed [today's date]).

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