Is CFB p.Phe286Leu (c.858C>G) pathogenic?

CFB p.Phe286Leu (c.858C>G) is classified Likely pathogenic in CFB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9765); Absent from gnomAD v4.1; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Phe286Leu (c.858C>G)?

CFB p.Phe286Leu (c.858C>G) is associated with atypical hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Phe286Leu (c.858C>G) in the general population?

CFB p.Phe286Leu (c.858C>G) is absent from gnomAD v4.1 (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

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

What do computational predictors say about CFB p.Phe286Leu (c.858C>G)?

AlphaMissense predicts likely pathogenic (score 0.9765) — an in-silico prediction, not a clinical call.

CFB p.Phe286Leu

c.858C>G · rs117905900 · VCV16079

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9765 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.9765	likely pathogenic ✓ concordant with ClinVar · top 6% in CFB
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -11.59	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 1.4	GERP -0.48, phastCons 1
Overall
CADD	23.9	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: CFB
Protein: p.Phe286Leu
Coding: c.858C>G
MANE Select: NM_001710
dbSNP: rs117905900
Type: single nucleotide variant
Location: chr6:31948042 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 286: an α-helix; a UniProt-annotated variant site (in ahus4; gain-of-function mutation that results in enhanced formation of the c3bbb); the vwfa domain

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

Disease context

atypical hemolytic-uremic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with B factor anomaly

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CFB p.Phe286= Benign/Likely benign ★★ same residue
CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg138Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg138Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg379Cys Uncertain significance ★★ ⚠ same condition
CFB p.Gln256Ter Uncertain significance ★★ same condition
CFB p.Glu601Lys 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/cfb-p-phe286leu (accessed [today's date]).

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