Is CFB p.Phe286= (c.858C>T) pathogenic?

CFB p.Phe286= (c.858C>T) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.95%, amr); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

How common is CFB p.Phe286= (c.858C>T) in the general population?

CFB p.Phe286= (c.858C>T) is low-frequency (popmax 3.95%, amr) (gnomAD).

CFB p.Phe286=

Q: What condition is associated with CFB p.Phe286= (c.858C>T)?

CFB p.Phe286= (c.858C>T) is associated with atypical hemolytic-uremic syndrome with B factor anomaly, atypical hemolytic-uremic syndrome (ClinVar).

c.858C>T · rs117905900 · VCV356281

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.95%, amr)

Conditions

atypical hemolytic-uremic syndrome with B 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 1.4	GERP -0.48, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.95% Admixed American · 2,369/60,028 alleles

Filtering AF 3.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.76%

Overall 0.259% 4,183/1,614,186 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.95%	25
East Asian	3.59%	28
Remaining individualsnot grpmax-eligible	0.253%	396
Middle Eastern	0.0495%	2,021
South Asian	0.0231%	4,337
African / African-American	0.00266%	37,525
European (non-Finnish)	0.00153%	65,557

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: CFB
Protein: p.Phe286=
Coding: c.858C>T
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 with B factor anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome

Similar variants

CFB p.Phe286Leu Likely pathogenic ★ 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-phe286 (accessed [today's date]).

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