Is CFB c.658+7T>C pathogenic?

CFB c.658+7T>C is classified Conflicting classifications of pathogenicity in CFB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-27). Rare (popmax 0.147%, afr); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

What condition is associated with CFB c.658+7T>C?

CFB c.658+7T>C is associated with atypical hemolytic-uremic syndrome with B factor anomaly, age related macular degeneration 14, complement factor b deficiency (ClinVar).

How common is CFB c.658+7T>C in the general population?

CFB c.658+7T>C is rare (popmax 0.147%, afr) (gnomAD).

CFB c.658+7T>C

rs541260302 · VCV992561

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, afr)

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
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -3.2, phastCons 0.023
Non-coding constraint	Z 5.30	1 kb window · o/e 0.69 · regional · uncalibrated
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% African / African-American · 110/75,024 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00719% 116/1,612,892 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.147%	682
Admixed American	0.005%	20,006
Remaining individualsnot grpmax-eligible	0.0048%	20,828

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
Coding: c.658+7T>C
MANE Select: NM_001710
dbSNP: rs541260302
Type: single nucleotide variant
Location: chr6:31947528 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB

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: age related macular degeneration 14 complement factor b deficiency

Similar variants

CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Gln256Ter Uncertain significance ★★ same condition
CFB p.Glu621Lys Uncertain significance ★★ ⚠ same condition
CFB p.His508Gln Uncertain significance ★★ ⚠ same condition
CFB p.Lys306Arg Uncertain significance ★★ ⚠ same condition
CFB p.Pro168Leu Uncertain significance ★★ ⚠ same condition
CFB p.Pro33Ala 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-c-658-plus-7t-c (accessed [today's date]).

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