Is CFB p.Glu232Lys (c.694G>A) pathogenic?

CFB p.Glu232Lys (c.694G>A) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00458%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Glu232Lys (c.694G>A)?

CFB p.Glu232Lys (c.694G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Glu232Lys (c.694G>A) in the general population?

CFB p.Glu232Lys (c.694G>A) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CFB p.Glu232Lys (c.694G>A)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

CFB p.Glu232Lys

c.694G>A · VCV3491516

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Overall
CADD	25.6	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 0.00458% European (non-Finnish) · 54/1,180,046 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.0036% 58/1,613,178 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,853
East Asian	0.00445%	22,448
Admixed American	0.00333%	30,004

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.Glu232Lys
Coding: c.694G>A
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31947777 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 232: an α-helix

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.Glu232Ala Uncertain significance ★ ⚠ same residue
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

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-glu232lys (accessed [today's date]).

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