Is CFB p.Ile550Thr (c.1649T>C) pathogenic?

CFB p.Ile550Thr (c.1649T>C) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.0848); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Ile550Thr (c.1649T>C)?

CFB p.Ile550Thr (c.1649T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Ile550Thr (c.1649T>C) in the general population?

CFB p.Ile550Thr (c.1649T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CFB p.Ile550Thr (c.1649T>C)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

CFB p.Ile550Thr

c.1649T>C · VCV3266575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 6.85e-05% 1/1,460,762 alleles · very rare

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.Ile550Thr
Coding: c.1649T>C
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31950643 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 550: a β-strand; a disulfide bond; the peptidase s1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFB p.Ile550= Likely benign ★ same residue
CFB p.Ala162Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala289Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same condition
CFB p.Arg117Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg193Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg419Lys Uncertain significance ★★ ⚠ same condition
CFB p.Arg642Gln 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-ile550thr (accessed [today's date]).

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