Is CFB p.Arg32Trp (c.94C>T) pathogenic?

CFB p.Arg32Trp (c.94C>T) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.084); Common (popmax 33.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

What condition is associated with CFB p.Arg32Trp (c.94C>T)?

CFB p.Arg32Trp (c.94C>T) is associated with atypical hemolytic-uremic syndrome with B factor anomaly, age related macular degeneration 14, complement factor b deficiency (ClinVar).

What do computational predictors say about CFB p.Arg32Trp (c.94C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

CFB p.Arg32Trp

Q: How common is CFB p.Arg32Trp (c.94C>T) in the general population?

CFB p.Arg32Trp (c.94C>T) is common (popmax 33.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.94C>T · rs12614 · VCV16076

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 33.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome with B factor anomaly

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -7.92	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 -2.4	GERP -3.5
Overall
CADD	15.54	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 33.4% African / African-American · 25,067/74,960 alleles

Filtering AF 33.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 33%

Overall 10.9% 175,694/1,612,892 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.4%	3
South Asian	20.3%	5
Middle Eastern	19.4%	5
Finnishnot grpmax-eligible	15.5%	6
Remaining individualsnot grpmax-eligible	11%	9
Admixed American	10.8%	9
Ashkenazi Jewishnot grpmax-eligible	9.34%	11
Amishnot grpmax-eligible	8.99%	11
European (non-Finnish)	8.64%	12
East Asian	6.86%	15

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.Arg32Trp
Coding: c.94C>T
MANE Select: NM_001710
dbSNP: rs12614
Type: single nucleotide variant
Location: chr6:31946402 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 32: a UniProt-annotated variant site (in allele s; may be associated with a reduced risk for age-related macular degeneration); a UniProt-annotated variant site (in)

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

Disease context

atypical hemolytic-uremic syndrome with B factor anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 14 complement factor b deficiency atypical hemolytic-uremic syndrome focal segmental glomerulosclerosis

Similar variants

CFB p.Arg32Gly Uncertain significance ★ ⚠ same residue
CFB p.Arg32Ter Uncertain significance ★ 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.Arg203Gln 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-arg32trp (accessed [today's date]).

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