Is CFB p.Lys729Arg (c.2186A>G) pathogenic?

CFB p.Lys729Arg (c.2186A>G) is classified Likely benign in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.0853%, afr); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Lys729Arg (c.2186A>G)?

CFB p.Lys729Arg (c.2186A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Lys729Arg (c.2186A>G) in the general population?

CFB p.Lys729Arg (c.2186A>G) is ultra-rare (popmax 0.0853%, afr) (gnomAD).

What do computational predictors say about CFB p.Lys729Arg (c.2186A>G)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

CFB p.Lys729Arg

c.2186A>G · rs11541541 · VCV1578948

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0853%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.50	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 -0.29	GERP -3.7
Overall
CADD	0.14	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 0.0853% African / African-American · 64/75,050 alleles

Filtering AF 0.0685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0624%

Overall 0.00508% 82/1,613,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0853%	1,173
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Admixed American	0.00666%	15,008
European (non-Finnish)	0.000508%	196,674

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.Lys729Arg
Coding: c.2186A>G
MANE Select: NM_001710
dbSNP: rs11541541
Type: single nucleotide variant
Location: chr6:31951921 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 729: an α-helix; 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

CFB p.Ala162Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala289Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same condition
CFB p.Arg117Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg193Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg419Lys Uncertain significance ★★ ⚠ same condition
CFB p.Arg642Gln Uncertain significance ★★ ⚠ same condition
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-lys729arg (accessed [today's date]).

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