Is CFB p.Lys306Arg (c.917A>G) pathogenic?

CFB p.Lys306Arg (c.917A>G) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: likely benign (0.0741); Very rare (popmax 0.00525%, nfe); Associated with macular degeneration.

What condition is associated with CFB p.Lys306Arg (c.917A>G)?

CFB p.Lys306Arg (c.917A>G) is associated with macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Lys306Arg (c.917A>G) in the general population?

CFB p.Lys306Arg (c.917A>G) is very rare (popmax 0.00525%, nfe) (gnomAD).

What do computational predictors say about CFB p.Lys306Arg (c.917A>G)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

CFB p.Lys306Arg

c.917A>G · rs374738591 · VCV906167

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macular degeneration

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.30	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 1.5	GERP -1.6, phastCons 1
Overall
CADD	12.72	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 0.00525% European (non-Finnish) · 62/1,180,052 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.0039% 63/1,614,114 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,033
African / African-American	0.00133%	74,932

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.Lys306Arg
Coding: c.917A>G
MANE Select: NM_001710
dbSNP: rs374738591
Type: single nucleotide variant
Location: chr6:31948393 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 306: the vwfa domain

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 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.Pro168Leu Uncertain significance ★★ ⚠ same condition
CFB p.Pro33Ala Uncertain significance ★★ ⚠ same condition
CFB p.Tyr588His Uncertain significance ★★ ⚠ same condition
CFB p.Val675Met 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-lys306arg (accessed [today's date]).

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