Is CFB p.Cys596= (c.1788T>C) pathogenic?

CFB p.Cys596= (c.1788T>C) is classified Likely benign in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). Very rare (popmax 0.00167%, amr).

How common is CFB p.Cys596= (c.1788T>C) in the general population?

CFB p.Cys596= (c.1788T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

CFB p.Cys596=

c.1788T>C · rs1771719454 · VCV2838921

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.504	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.44	GERP -3.8, phastCons 0.16
Overall
CADD	7.467	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,994 alleles

Overall 6.2e-05% 1/1,612,844 alleles · very rare exomes 0/1,460,774 · genomes 1/152,070 · joint denominator

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.Cys596=
Coding: c.1788T>C
MANE Select: NM_001710
dbSNP: rs1771719454
Type: single nucleotide variant
Location: chr6:31950877 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 596: a disulfide bond; the peptidase s1 domain

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

Similar variants

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
CFB p.Arg138Gln Uncertain significance ★★ ⚠ same type
CFB p.Arg138Trp 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-cys596 (accessed [today's date]).

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