Is CFB p.Arg32Gln (c.95G>A) pathogenic?

CFB p.Arg32Gln (c.95G>A) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.064); Common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with complement component 2 deficiency.

What condition is associated with CFB p.Arg32Gln (c.95G>A)?

CFB p.Arg32Gln (c.95G>A) is associated with complement component 2 deficiency, atypical hemolytic-uremic syndrome with B factor anomaly, age related macular degeneration 14 (ClinVar).

What do computational predictors say about CFB p.Arg32Gln (c.95G>A)?

AlphaMissense predicts likely benign (score 0.064) — an in-silico prediction, not a clinical call.

CFB p.Arg32Gln

Q: How common is CFB p.Arg32Gln (c.95G>A) in the general population?

CFB p.Arg32Gln (c.95G>A) is common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Immunodeficiency due to a classical component pathway complement deficiency inherited?

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

c.95G>A · rs641153 · VCV16075

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.064 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 2 deficiency

Computational evidence

Protein change
AlphaMissense	0.064	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -3.5
Overall
CADD	0.036	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 18.9% African / African-American · 14,195/74,962 alleles

Filtering AF 18.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.6%

Overall 9.89% 159,488/1,612,870 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.9%	5
South Asian	14.8%	7
Remaining individualsnot grpmax-eligible	10.9%	9
European (non-Finnish)	9.39%	11
Admixed American	8.02%	12
East Asian	7.23%	14
Middle Eastern	7.01%	14
Finnishnot grpmax-eligible	6.38%	16
Ashkenazi Jewishnot grpmax-eligible	5.57%	18
Amishnot grpmax-eligible	4.61%	22

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.Arg32Gln
Coding: c.95G>A
MANE Select: NM_000063 · reported on NM_001710
dbSNP: rs641153
Type: single nucleotide variant
Location: chr6:31946403 (GRCh38)

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

Disease context

complement component 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with B factor anomaly age related macular degeneration 14 atypical hemolytic-uremic syndrome focal segmental glomerulosclerosis

For Immunodeficiency due to a classical component pathway complement deficiency (Orphanet):

Inheritance: Autosomal recessive

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-arg32gln (accessed [today's date]).

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