Is CFB p.Lys565Glu (c.1693A>G) pathogenic?

CFB p.Lys565Glu (c.1693A>G) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1276); Low-frequency (popmax 3.38%, afr); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Lys565Glu (c.1693A>G)?

CFB p.Lys565Glu (c.1693A>G) is associated with atypical hemolytic-uremic syndrome, macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Lys565Glu (c.1693A>G) in the general population?

CFB p.Lys565Glu (c.1693A>G) is low-frequency (popmax 3.38%, afr) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFB p.Lys565Glu (c.1693A>G)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CFB p.Lys565Glu

c.1693A>G · rs4151659 · VCV356292

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.38%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -9.10	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 4.7	GERP 1.9, phastCons 0.98
Overall
CADD	17.87	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 3.38% African / African-American · 2,535/75,026 alleles

Filtering AF 3.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.22%

Overall 1.24% 20,062/1,613,060 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.38%	30
Admixed American	2.02%	49
European (non-Finnish)	1.27%	78
Remaining individualsnot grpmax-eligible	1.15%	87
Ashkenazi Jewishnot grpmax-eligible	1.11%	90
Middle Eastern	1.06%	95
Finnishnot grpmax-eligible	0.188%	533
Amishnot grpmax-eligible	0.11%	912
South Asian	0.0494%	2,024

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.Lys565Glu
Coding: c.1693A>G
MANE Select: NM_001710
dbSNP: rs4151659
Type: single nucleotide variant
Location: chr6:31950687 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 565: an α-helix; a disulfide bond; a UniProt-annotated variant site (in); the peptidase s1 domain

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

Disease context

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

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

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

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
CFB p.Glu601Lys Uncertain significance ★★ ⚠ same condition
CFB p.Glu621Lys 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-lys565glu (accessed [today's date]).

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