Is CFB p.Val577Ala (c.1730T>C) pathogenic?

CFB p.Val577Ala (c.1730T>C) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: ambiguous (0.4675); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFB p.Val577Ala (c.1730T>C)?

CFB p.Val577Ala (c.1730T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Val577Ala (c.1730T>C) in the general population?

CFB p.Val577Ala (c.1730T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFB p.Val577Ala (c.1730T>C)?

AlphaMissense predicts ambiguous (score 0.4675) — an in-silico prediction, not a clinical call.

CFB p.Val577Ala

c.1730T>C · rs1451018034 · VCV2478231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4675 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4675	ambiguous
REVEL	0.259	benign-leaning
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Overall
CADD	25.0	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.Val577Ala
Coding: c.1730T>C
MANE Select: NM_001710
dbSNP: rs1451018034
Type: single nucleotide variant
Location: chr6:31950724 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 577: a disulfide bond; the peptidase s1 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.Val577Ile Uncertain significance ★★ ⚠ same residue
CFB p.Ala162Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala289Val 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

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-val577ala (accessed [today's date]).

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