Is CFB p.Asp651Glu (c.1953T>G) pathogenic?

CFB p.Asp651Glu (c.1953T>G) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0834); Low-frequency (popmax 2.33%, afr); Associated with macular degeneration.

What condition is associated with CFB p.Asp651Glu (c.1953T>G)?

CFB p.Asp651Glu (c.1953T>G) is associated with macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly, atypical hemolytic-uremic syndrome (ClinVar).

How common is CFB p.Asp651Glu (c.1953T>G) in the general population?

CFB p.Asp651Glu (c.1953T>G) is low-frequency (popmax 2.33%, afr) (gnomAD).

What do computational predictors say about CFB p.Asp651Glu (c.1953T>G)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

CFB p.Asp651Glu

c.1953T>G · rs4151660 · VCV903887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.33%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macular degeneration

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -5.97	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 -5.2	GERP -3.5
Overall
CADD	0.029	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 2.33% African / African-American · 1,750/75,028 alleles

Filtering AF 2.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 0.121% 1,954/1,613,184 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.33%	43
Admixed American	0.133%	750
Remaining individualsnot grpmax-eligible	0.131%	762
Middle Eastern	0.033%	3,031
South Asian	0.00988%	10,120
European (non-Finnish)	0.00263%	38,065

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.Asp651Glu
Coding: c.1953T>G
MANE Select: NM_001710
dbSNP: rs4151660
Type: single nucleotide variant
Location: chr6:31951241 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 651: a β-strand; a UniProt-annotated variant site (in); the peptidase s1 domain

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

Disease context

macular degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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
CFB p.Glu621Lys 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-asp651glu (accessed [today's date]).

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