Is CFB p.Glu549Asp (c.1647G>C) pathogenic?

CFB p.Glu549Asp (c.1647G>C) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.0909); Very rare (popmax 8.47e-05%, nfe).

How common is CFB p.Glu549Asp (c.1647G>C) in the general population?

CFB p.Glu549Asp (c.1647G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CFB p.Glu549Asp (c.1647G>C)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

CFB p.Glu549Asp

c.1647G>C · rs771770314 · VCV2786971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -6.45	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 -0.54	GERP -3.2
Overall
CADD	5.589	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 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.2e-05% 1/1,613,088 alleles · very rare exomes 1/1,460,760 · genomes 0/152,328 · joint denominator

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.Glu549Asp
Coding: c.1647G>C
MANE Select: NM_001710
dbSNP: rs771770314
Type: single nucleotide variant
Location: chr6:31950641 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 549: an α-helix; the peptidase s1 domain

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

Similar variants

CFB p.Glu549Gln Uncertain significance ★★ ⚠ same residue
CFB p.Glu549= Likely benign ★ same residue
CFB c.2140-1G>C Uncertain significance ★★ same type
CFB c.-3G>A Uncertain significance ★★ same type
CFB p.Ala162Val Uncertain significance ★★ ⚠ same type
CFB p.Ala289Val Uncertain significance ★★ same type
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same type
CFB p.Arg117Trp Uncertain significance ★★ ⚠ same type

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-glu549asp (accessed [today's date]).

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