Is CFB p.Gly252Ser (c.754G>A) pathogenic?

CFB p.Gly252Ser (c.754G>A) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0564); Low-frequency (popmax 3.81%, nfe); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFB p.Gly252Ser (c.754G>A)?

CFB p.Gly252Ser (c.754G>A) is associated with atypical hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.Gly252Ser (c.754G>A) in the general population?

CFB p.Gly252Ser (c.754G>A) is low-frequency (popmax 3.81%, nfe) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

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

What do computational predictors say about CFB p.Gly252Ser (c.754G>A)?

AlphaMissense predicts likely benign (score 0.0564) — an in-silico prediction, not a clinical call.

CFB p.Gly252Ser

c.754G>A · rs4151651 · VCV356280

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0564 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.81%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.0564	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP -0.049, phastCons 0.92
Overall
CADD	15.79	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

Grpmax group 3.81% European (non-Finnish) · 44,905/1,180,004 alleles

Filtering AF 3.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.76%

Overall 3.13% 50,591/1,613,848 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.81%	26
Remaining individualsnot grpmax-eligible	3.07%	33
Finnishnot grpmax-eligible	2.89%	35
Admixed American	1.4%	71
Amishnot grpmax-eligible	1.32%	76
Ashkenazi Jewishnot grpmax-eligible	1.26%	79
African / African-American	0.624%	160
South Asian	0.233%	430
Middle Eastern	0.182%	551
East Asian	0.0267%	3,740

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.Gly252Ser
Coding: c.754G>A
MANE Select: NM_001710
dbSNP: rs4151651
Type: single nucleotide variant
Location: chr6:31947837 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 252: a UniProt-annotated variant site (in)

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.Gly252Asp 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-gly252ser (accessed [today's date]).

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