Is CFB p.Asp547Glu (c.1641C>G) pathogenic?

CFB p.Asp547Glu (c.1641C>G) is classified Conflicting classifications of pathogenicity in CFB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1016); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Asp547Glu (c.1641C>G)?

CFB p.Asp547Glu (c.1641C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Asp547Glu (c.1641C>G) in the general population?

CFB p.Asp547Glu (c.1641C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CFB p.Asp547Glu (c.1641C>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

CFB p.Asp547Glu

c.1641C>G · rs999669276 · VCV1488403

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -6.06	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 -0.37	GERP -3.8
Overall
CADD	0.364	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 0.005% Admixed American · 3/59,992 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,612,880 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Asp547Glu
Coding: c.1641C>G
MANE Select: NM_001710
dbSNP: rs999669276
Type: single nucleotide variant
Location: chr6:31950635 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 547: an α-helix; a disulfide bond; the peptidase s1 domain

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

Similar variants

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CFB p.Arg730Trp 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-asp547glu (accessed [today's date]).

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