Is CFB p.Ala289Val (c.866C>T) pathogenic?

CFB p.Ala289Val (c.866C>T) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.5413); Very rare (popmax 0.000847%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Ala289Val (c.866C>T)?

CFB p.Ala289Val (c.866C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Ala289Val (c.866C>T) in the general population?

CFB p.Ala289Val (c.866C>T) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about CFB p.Ala289Val (c.866C>T)?

AlphaMissense predicts ambiguous (score 0.5413) — an in-silico prediction, not a clinical call.

CFB p.Ala289Val

c.866C>T · rs140338493 · VCV1521835

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5413	ambiguous
REVEL	0.597	indeterminate
SaProt	LLR -7.18	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	26.2	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 0.000847% European (non-Finnish) · 10/1,180,010 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000684% 10/1,461,890 alleles · very rare

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.Ala289Val
Coding: c.866C>T
MANE Select: NM_001710
dbSNP: rs140338493
Type: single nucleotide variant
Location: chr6:31948050 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 289: an α-helix; the vwfa 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.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
CFB p.Arg74Cys 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-ala289val (accessed [today's date]).

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