Is CFB p.Pro33Ala (c.97C>G) pathogenic?

CFB p.Pro33Ala (c.97C>G) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.0702); Ultra-rare (popmax 0.036%, afr); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Pro33Ala (c.97C>G)?

CFB p.Pro33Ala (c.97C>G) is associated with Inborn genetic diseases, atypical hemolytic-uremic syndrome with B factor anomaly, complement factor b deficiency (ClinVar).

How common is CFB p.Pro33Ala (c.97C>G) in the general population?

CFB p.Pro33Ala (c.97C>G) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about CFB p.Pro33Ala (c.97C>G)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

CFB p.Pro33Ala

c.97C>G · rs367892230 · VCV1940636

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -5.43	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 -1.3	GERP -1.8
Overall
CADD	1.264	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 0.036% African / African-American · 27/75,048 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00174% 28/1,613,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,780
Admixed American	0.00167%	60,034

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.Pro33Ala
Coding: c.97C>G
MANE Select: NM_001710
dbSNP: rs367892230
Type: single nucleotide variant
Location: chr6:31946405 (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

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

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

Similar variants

CFB c.-3G>A Uncertain significance ★★ same condition
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.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg419Lys 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-pro33ala (accessed [today's date]).

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