Is CFB p.Ile469Phe (c.1405A>T) pathogenic?

CFB p.Ile469Phe (c.1405A>T) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: ambiguous (0.4831); Absent from gnomAD v4.1.

How common is CFB p.Ile469Phe (c.1405A>T) in the general population?

CFB p.Ile469Phe (c.1405A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFB p.Ile469Phe (c.1405A>T)?

AlphaMissense predicts ambiguous (score 0.4831) — an in-silico prediction, not a clinical call.

CFB p.Ile469Phe

c.1405A>T · rs2151785423 · VCV1442068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4831	ambiguous
REVEL	0.45	indeterminate
SaProt	LLR -7.48	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.2	GERP -1.6, phastCons 1
Overall
CADD	22.8	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

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.Ile469Phe
Coding: c.1405A>T
MANE Select: NM_001710
dbSNP: rs2151785423
Type: single nucleotide variant
Location: chr6:31949554 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 469: the vwfa domain

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

Similar variants

CFB p.Ile469= Uncertain significance ★ same residue
CFB p.Ile469Met Conflicting classifications of pathogenicity ★ ⚠ 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-ile469phe (accessed [today's date]).

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