Is CFB p.Asp447Glu (c.1341C>A) pathogenic?

CFB p.Asp447Glu (c.1341C>A) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-07). AlphaMissense: likely benign (0.093); Very rare (popmax 0.0022%, sas); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

What condition is associated with CFB p.Asp447Glu (c.1341C>A)?

CFB p.Asp447Glu (c.1341C>A) is associated with atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Asp447Glu (c.1341C>A) in the general population?

CFB p.Asp447Glu (c.1341C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CFB p.Asp447Glu (c.1341C>A)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

CFB p.Asp447Glu

c.1341C>A · VCV4876732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome with B factor anomaly

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -3.46	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 0.037	GERP -2.8, phastCons 0.004
Overall
CADD	8.607	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 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000248% 4/1,613,816 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,922

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.Asp447Glu
Coding: c.1341C>A
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31949490 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 447: the vwfa domain

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

Similar variants

CFB p.Asp447Tyr Uncertain significance ★★ ⚠ same residue
CFB p.Asp447= Likely benign ★ same residue
CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg203Gln Uncertain significance ★★ same condition
CFB p.Glu621Lys Uncertain significance ★★ ⚠ same condition
CFB p.His508Gln Uncertain significance ★★ ⚠ same condition
CFB p.Lys306Arg Uncertain significance ★★ ⚠ same condition
CFB p.Pro168Leu 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-asp447glu (accessed [today's date]).

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