Is CFB p.Arg203Gln (c.608G>A) pathogenic?

CFB p.Arg203Gln (c.608G>A) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.4657); Very rare (popmax 0.0011%, sas); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Arg203Gln (c.608G>A)?

CFB p.Arg203Gln (c.608G>A) is associated with atypical hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Arg203Gln (c.608G>A) in the general population?

CFB p.Arg203Gln (c.608G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFB p.Arg203Gln (c.608G>A)?

AlphaMissense predicts ambiguous (score 0.4657) — an in-silico prediction, not a clinical call.

CFB p.Arg203Gln

c.608G>A · rs745794224 · VCV2136371

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.4657	ambiguous
REVEL	0.457	indeterminate
SaProt	LLR -11.76	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,460,754 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	0.000424%	236,002

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.Arg203Gln
Coding: c.608G>A
MANE Select: NM_001710
dbSNP: rs745794224
Type: single nucleotide variant
Location: chr6:31947471 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 203: a disulfide bond; a UniProt-annotated variant site (in ahus4); the sushi 3 domain; a β-strand

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

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

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.Arg203Leu Uncertain significance ★ ⚠ same residue
CFB p.Arg203Ter Uncertain significance ★ same residue
CFB p.Arg203= Likely benign ★ 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.Arg379Cys Uncertain significance ★★ ⚠ same condition
CFB p.Gln256Ter 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-arg203gln (accessed [today's date]).

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