Is CFB p.Gln728Ter (c.2182C>T) pathogenic?

CFB p.Gln728Ter (c.2182C>T) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). Absent from gnomAD v4.1; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Gln728Ter (c.2182C>T)?

CFB p.Gln728Ter (c.2182C>T) is associated with atypical hemolytic-uremic syndrome (ClinVar).

How common is CFB p.Gln728Ter (c.2182C>T) in the general population?

CFB p.Gln728Ter (c.2182C>T) 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.

CFB p.Gln728Ter

c.2182C>T · VCV4280418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.43	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.83	GERP -2
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Gln728Ter
Coding: c.2182C>T
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31951917 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 728: an α-helix; the peptidase s1 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

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.Gln728= Uncertain significance ★ same residue
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
CFB p.Ser284Asn 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-gln728ter (accessed [today's date]).

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