Is CFB p.Arg546= (c.1636C>A) pathogenic?

CFB p.Arg546= (c.1636C>A) is classified Likely benign in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). Very rare (popmax 0.000763%, nfe).

How common is CFB p.Arg546= (c.1636C>A) in the general population?

CFB p.Arg546= (c.1636C>A) is very rare (popmax 0.000763%, nfe) (gnomAD).

CFB p.Arg546=

c.1636C>A · VCV4693432

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -2.3, phastCons 0.75
Overall
CADD	4.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,024 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,810 alleles · very rare exomes 8/1,460,708 · genomes 1/152,102 · 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.Arg546=
Coding: c.1636C>A
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31950630 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 546: an α-helix; the peptidase s1 domain

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

Similar variants

CFB p.Arg546Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CFB p.Arg546Trp Uncertain significance ★ ⚠ 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-arg546 (accessed [today's date]).

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