Is CFB p.Tyr135= (c.405C>T) pathogenic?

CFB p.Tyr135= (c.405C>T) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.21%, afr); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

How common is CFB p.Tyr135= (c.405C>T) in the general population?

CFB p.Tyr135= (c.405C>T) is low-frequency (popmax 3.21%, afr) (gnomAD).

CFB p.Tyr135=

Q: What condition is associated with CFB p.Tyr135= (c.405C>T)?

CFB p.Tyr135= (c.405C>T) is associated with atypical hemolytic-uremic syndrome with B factor anomaly, atypical hemolytic-uremic syndrome (ClinVar).

c.405C>T · rs4151650 · VCV356271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.21%, afr)

Conditions

atypical hemolytic-uremic syndrome with B factor anomaly

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>G here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.23	GERP -3.4, phastCons 0.001
Overall
CADD	7.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.21% African / African-American · 2,411/75,026 alleles

Filtering AF 3.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.06%

Overall 0.246% 3,969/1,613,052 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.21%	31
Admixed American	0.686%	146
Remaining individualsnot grpmax-eligible	0.36%	278
Middle Eastern	0.297%	337
European (non-Finnish)	0.071%	1,408
East Asian	0.0423%	2,362
South Asian	0.0296%	3,373
Finnishnot grpmax-eligible	0.0238%	4,196
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402

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.Tyr135=
Coding: c.405C>T
MANE Select: NM_001710
dbSNP: rs4151650
Type: single nucleotide variant
Location: chr6:31947113 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 135: a disulfide bond; the sushi 2 domain

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

Disease context

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

Also linked: 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-tyr135 (accessed [today's date]).

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