Is CFB p.Gln219Leu (c.656A>T) pathogenic?

CFB p.Gln219Leu (c.656A>T) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1533); Absent from gnomAD v4.1; Associated with macular degeneration.

What condition is associated with CFB p.Gln219Leu (c.656A>T)?

CFB p.Gln219Leu (c.656A>T) is associated with macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Gln219Leu (c.656A>T) in the general population?

CFB p.Gln219Leu (c.656A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFB p.Gln219Leu (c.656A>T)?

AlphaMissense predicts likely benign (score 0.1533) — an in-silico prediction, not a clinical call.

CFB p.Gln219Leu

c.656A>T · rs886061295 · VCV356276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1533 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

macular degeneration

Computational evidence

Protein change
AlphaMissense	0.1533	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.38	loss · gain 0.17 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 0.9, phastCons 1
Overall
CADD	26.2	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.Gln219Leu
Coding: c.656A>T
MANE Select: NM_001710
dbSNP: rs886061295
Type: single nucleotide variant
Location: chr6:31947519 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 219: the sushi 3 domain; a β-strand

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

Disease context

macular degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with B factor anomaly

Similar variants

CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Glu621Lys Uncertain significance ★★ ⚠ same condition
CFB p.His508Gln Uncertain significance ★★ ⚠ same condition
CFB p.Lys306Arg Uncertain significance ★★ ⚠ same condition
CFB p.Pro168Leu Uncertain significance ★★ ⚠ same condition
CFB p.Pro33Ala Uncertain significance ★★ ⚠ same condition
CFB p.Tyr588His 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-gln219leu (accessed [today's date]).

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