Is CFB p.His107= (c.321C>T) pathogenic?

CFB p.His107= (c.321C>T) is classified Conflicting classifications of pathogenicity in CFB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-04). Ultra-rare (popmax 0.0111%, eas); Associated with macular degeneration.

What condition is associated with CFB p.His107= (c.321C>T)?

CFB p.His107= (c.321C>T) is associated with macular degeneration, atypical hemolytic-uremic syndrome with B factor anomaly (ClinVar).

How common is CFB p.His107= (c.321C>T) in the general population?

CFB p.His107= (c.321C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

CFB p.His107=

c.321C>T · rs767428982 · VCV356270

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

macular degeneration

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 Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP -0.79, phastCons 1
Overall
CADD	9.803	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,880 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00248% 40/1,612,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,976
Remaining individualsnot grpmax-eligible	0.0096%	10,412
Admixed American	0.00667%	15,001
South Asian	0.00329%	30,361
African / African-American	0.00267%	37,438
European (non-Finnish)	0.00169%	59,002

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.His107=
Coding: c.321C>T
MANE Select: NM_001710
dbSNP: rs767428982
Type: single nucleotide variant
Location: chr6:31947029 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 107: a disulfide bond; the sushi 2 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

Similar variants

CFB c.-3G>A Uncertain significance ★★ same condition
CFB p.Arg203Gln Uncertain significance ★★ ⚠ same condition
CFB p.Glu621Lys Uncertain significance ★★ ⚠ same condition
CFB p.His508Gln 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
CFB p.Tyr588His 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-his107 (accessed [today's date]).

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