Is CFB p.His508= (c.1524C>T) pathogenic?

CFB p.His508= (c.1524C>T) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-05). Rare (popmax 0.379%, mid); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

What condition is associated with CFB p.His508= (c.1524C>T)?

CFB p.His508= (c.1524C>T) is associated with atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.His508= (c.1524C>T) in the general population?

CFB p.His508= (c.1524C>T) is rare (popmax 0.379%, mid) (gnomAD).

CFB p.His508=

c.1524C>T · rs138207668 · VCV356290

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.379%, mid)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.1
Overall
CADD	0.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.379% Middle Eastern · 23/6,062 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.327%

Overall 0.238% 3,832/1,612,978 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.47%	213
Middle Easterngrpmax	0.379%	264
South Asian	0.372%	269
Admixed American	0.303%	330
Remaining individualsnot grpmax-eligible	0.25%	401
European (non-Finnish)	0.23%	434
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
East Asian	0.0891%	1,122
African / African-American	0.0413%	2,420

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His508=
Coding: c.1524C>T
MANE Select: NM_001710
dbSNP: rs138207668
Type: single nucleotide variant
Location: chr6:31950303 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 508: a disulfide bond; the peptidase s1 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

Similar variants

CFB p.His508Gln Uncertain significance ★★ ⚠ same residue
CFB p.His508Asn Uncertain significance ★ ⚠ same residue
CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Glu621Lys Uncertain significance ★★ ⚠ same condition
CFB p.Lys306Arg Uncertain significance ★★ ⚠ same condition
CFB p.Pro168Leu Uncertain significance ★★ ⚠ same condition
CFB p.Pro33Ala 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-his508 (accessed [today's date]).

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