Is CFB p.Pro168= (c.504G>A) pathogenic?

CFB p.Pro168= (c.504G>A) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-09-17). Common (popmax 5.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Pro168= (c.504G>A)?

CFB p.Pro168= (c.504G>A) is associated with atypical hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFB p.Pro168=

Q: How common is CFB p.Pro168= (c.504G>A) in the general population?

CFB p.Pro168= (c.504G>A) is common (popmax 5.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.504G>A · rs4151669 · VCV356273

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 5.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3
Overall
CADD	0.923	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.1% South Asian · 4,649/91,078 alleles

Filtering AF 4.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.93%

Overall 4.17% 67,272/1,612,954 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	5.5%	18
South Asiangrpmax	5.1%	20
European (non-Finnish)	4.48%	22
Remaining individualsnot grpmax-eligible	3.77%	27
Middle Eastern	2.66%	38
Ashkenazi Jewishnot grpmax-eligible	2.56%	39
Admixed American	2.31%	43
East Asian	1.66%	60
Amishnot grpmax-eligible	1.32%	76
African / African-American	1.24%	81

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro168=
Coding: c.504G>A
MANE Select: NM_001710
dbSNP: rs4151669
Type: single nucleotide variant
Location: chr6:31947367 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 168: a disulfide bond; the sushi 3 domain

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

Disease context

atypical hemolytic-uremic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CFB p.Pro168Leu Uncertain significance ★★ ⚠ same residue
CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg138Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg138Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg379Cys Uncertain significance ★★ ⚠ same condition
CFB p.Gln256Ter Uncertain significance ★★ same condition
CFB p.Glu601Lys 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-pro168 (accessed [today's date]).

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