Is CFB p.Glu97= (c.291G>A) pathogenic?

CFB p.Glu97= (c.291G>A) is classified Conflicting classifications of pathogenicity in CFB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0634%, nfe); Associated with macular degeneration.

What condition is associated with CFB p.Glu97= (c.291G>A)?

CFB p.Glu97= (c.291G>A) is associated with macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Glu97= (c.291G>A) in the general population?

CFB p.Glu97= (c.291G>A) is ultra-rare (popmax 0.0634%, nfe) (gnomAD).

CFB p.Glu97=

c.291G>A · rs138236643 · VCV356269

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0634%, nfe)

Conditions

macular degeneration

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -0.41, phastCons 0.88
Overall
CADD	8.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0634% European (non-Finnish) · 748/1,179,986 alleles

Filtering AF 0.0596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.0479% 771/1,608,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0634%	1,578
Remaining individualsnot grpmax-eligible	0.0288%	3,470
Admixed American	0.005%	19,996
African / African-American	0.00267%	37,463

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.Glu97=
Coding: c.291G>A
MANE Select: NM_001710
dbSNP: rs138236643
Type: single nucleotide variant
Location: chr6:31946599 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 97: a disulfide bond; the sushi 1 domain; a β-strand

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

Disease context

macular degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with B factor anomaly

Similar variants

CFB p.Glu97Asp Uncertain significance ★★ ⚠ 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
CFB p.Pro33Ala 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-glu97 (accessed [today's date]).

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