Is CFB p.Lys533Arg (c.1598A>G) pathogenic?

CFB p.Lys533Arg (c.1598A>G) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0864); Common (popmax 6.01%, sas) — too common for a highly-penetrant pathogenic allele; Associated with age related macular degeneration 14.

What condition is associated with CFB p.Lys533Arg (c.1598A>G)?

CFB p.Lys533Arg (c.1598A>G) is associated with age related macular degeneration 14, complement component 2 deficiency, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

What do computational predictors say about CFB p.Lys533Arg (c.1598A>G)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

CFB p.Lys533Arg

Q: How common is CFB p.Lys533Arg (c.1598A>G) in the general population?

CFB p.Lys533Arg (c.1598A>G) is common (popmax 6.01%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1598A>G · rs149101394 · VCV225313

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.01%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

age related macular degeneration 14

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.491	indeterminate
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.1, phastCons 1
Overall
CADD	19.88	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 6.01% South Asian · 5,474/91,086 alleles

Filtering AF 5.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.82%

Overall 0.48% 7,747/1,613,030 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	6.01%	17
African / African-American	1.07%	93
Remaining individualsnot grpmax-eligible	0.699%	143
East Asian	0.628%	159
Middle Eastern	0.544%	184
Admixed American	0.178%	561
European (non-Finnish)	0.0507%	1,973
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467

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.Lys533Arg
Coding: c.1598A>G
MANE Select: NM_001710
dbSNP: rs149101394
Type: single nucleotide variant
Location: chr6:31950377 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 533: a β-strand; a disulfide bond; a UniProt-annotated variant site (in ahus4; benign); the peptidase s1 domain

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

Disease context

Also linked: complement component 2 deficiency atypical hemolytic-uremic syndrome with B factor anomaly complement factor b deficiency atypical hemolytic-uremic syndrome

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-lys533arg (accessed [today's date]).

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