Is CFB p.Arg379Cys (c.1135C>T) pathogenic?

CFB p.Arg379Cys (c.1135C>T) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3615); Very rare (popmax 0.00668%, eas); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Arg379Cys (c.1135C>T)?

CFB p.Arg379Cys (c.1135C>T) is associated with atypical hemolytic-uremic syndrome (ClinVar).

How common is CFB p.Arg379Cys (c.1135C>T) in the general population?

CFB p.Arg379Cys (c.1135C>T) is very rare (popmax 0.00668%, eas) (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.Arg379Cys (c.1135C>T)?

AlphaMissense predicts ambiguous (score 0.3615) — an in-silico prediction, not a clinical call.

CFB p.Arg379Cys

c.1135C>T · rs781563498 · VCV2152008

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.3615	ambiguous
REVEL	0.586	indeterminate
SaProt	LLR -9.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.79, phastCons 0.98
Overall
CADD	27.0	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 0.00668% East Asian · 3/44,890 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00155% 25/1,612,600 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
South Asian	0.0022%	45,536
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.00144%	69,408
African / African-American	0.00134%	74,840

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.Arg379Cys
Coding: c.1135C>T
MANE Select: NM_001710
dbSNP: rs781563498
Type: single nucleotide variant
Location: chr6:31948928 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 379: an α-helix; the vwfa 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.Arg379= Benign/Likely benign ★★ same residue
CFB p.Arg379His 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.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-arg379cys (accessed [today's date]).

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