Is CFB p.Asp133= (c.399C>T) pathogenic?

CFB p.Asp133= (c.399C>T) is classified Likely benign in CFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-23). Very rare (popmax 0.00446%, eas).

How common is CFB p.Asp133= (c.399C>T) in the general population?

CFB p.Asp133= (c.399C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

CFB p.Asp133=

c.399C>T · rs769901381 · VCV1632932

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.5	GERP -3.4
Overall
CADD	6.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,868 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0013% 21/1,613,028 alleles · very rare exomes 21/1,460,764 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,434
South Asian	0.00329%	30,361
European (non-Finnish)	0.00136%	73,752

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.Asp133=
Coding: c.399C>T
MANE Select: NM_001710
dbSNP: rs769901381
Type: single nucleotide variant
Location: chr6:31947107 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 133: the sushi 2 domain

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

Similar variants

CFB p.Asp133Asn 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
CFB p.Arg138Gln 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-asp133 (accessed [today's date]).

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