Is CFB p.Glu40Gln (c.118G>C) pathogenic?

CFB p.Glu40Gln (c.118G>C) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-06). AlphaMissense: likely benign (0.0924); Absent from gnomAD v4.1.

How common is CFB p.Glu40Gln (c.118G>C) in the general population?

CFB p.Glu40Gln (c.118G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFB p.Glu40Gln (c.118G>C)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

CFB p.Glu40Gln

c.118G>C · rs1271096223 · VCV1376133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -6.62	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 3.5	GERP -1.9, phastCons 1
Overall
CADD	18.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFB
Protein: p.Glu40Gln
Coding: c.118G>C
MANE Select: NM_001710
dbSNP: rs1271096223
Type: single nucleotide variant
Location: chr6:31946426 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 40: a disulfide bond; the sushi 1 domain

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

Similar variants

CFB p.Glu40Lys Uncertain significance ⚠ same residue
CFB c.2140-1G>C Uncertain significance ★★ same type
CFB c.-3G>A Uncertain significance ★★ same type
CFB p.Ala162Val Uncertain significance ★★ ⚠ same type
CFB p.Ala289Val Uncertain significance ★★ ⚠ same type
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same type
CFB p.Arg117Trp Uncertain significance ★★ ⚠ same type
CFB p.Arg138Gln Uncertain significance ★★ ⚠ same type

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-glu40gln (accessed [today's date]).

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