Is CFB p.Val455= (c.1365C>T) pathogenic?

CFB p.Val455= (c.1365C>T) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). Common (popmax 12.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

What condition is associated with CFB p.Val455= (c.1365C>T)?

CFB p.Val455= (c.1365C>T) is associated with atypical hemolytic-uremic syndrome with B factor anomaly, atypical hemolytic-uremic syndrome, focal segmental glomerulosclerosis (ClinVar).

CFB p.Val455=

Q: How common is CFB p.Val455= (c.1365C>T) in the general population?

CFB p.Val455= (c.1365C>T) is common (popmax 12.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1365C>T · rs2072634 · VCV356287

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 12.3%, sas) — too common for a highly-penetrant pathogenic allele

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.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -3.3, phastCons 1
Overall
CADD	12.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.3% South Asian · 11,213/91,078 alleles

Filtering AF 12.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 12%

Overall 2.6% 41,981/1,613,554 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	12.3%	8
East Asian	6.62%	15
Remaining individualsnot grpmax-eligible	3.4%	29
Finnishnot grpmax-eligible	2.48%	40
European (non-Finnish)	1.84%	54
African / African-American	1.76%	57
Middle Eastern	1.72%	58
Ashkenazi Jewishnot grpmax-eligible	1.2%	84
Admixed American	0.905%	111
Amishnot grpmax-eligible	0.768%	130

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.Val455=
Coding: c.1365C>T
MANE Select: NM_001710
dbSNP: rs2072634
Type: single nucleotide variant
Location: chr6:31949514 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 455: a β-strand; the vwfa 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 focal segmental glomerulosclerosis

Similar variants

CFB p.Val455Ile Likely pathogenic ★ ⚠ 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-val455 (accessed [today's date]).

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