Is CFB p.Pro494= (c.1482A>G) pathogenic?

CFB p.Pro494= (c.1482A>G) is classified Benign in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-27). Ultra-rare (popmax 0.085%, amr).

How common is CFB p.Pro494= (c.1482A>G) in the general population?

CFB p.Pro494= (c.1482A>G) is ultra-rare (popmax 0.085%, amr) (gnomAD).

CFB p.Pro494=

c.1482A>G · rs759385828 · VCV1631472

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.085%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.9
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.085% Admixed American · 51/60,016 alleles

Filtering AF 0.0663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0598%

Overall 0.00341% 55/1,612,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.085%	1,177
Remaining individualsnot grpmax-eligible	0.0064%	15,618

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.Pro494=
Coding: c.1482A>G
MANE Select: NM_001710
dbSNP: rs759385828
Type: single nucleotide variant
Location: chr6:31950123 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 494: a disulfide bond; the peptidase s1 domain

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

Similar variants

CFB p.Pro494Gln Uncertain significance ★ ⚠ same residue
CFB p.Pro494Thr 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

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-pro494 (accessed [today's date]).

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