Is CFB p.Val516= (c.1548G>A) pathogenic?

CFB p.Val516= (c.1548G>A) is classified Benign/Likely benign in CFB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-18). Ultra-rare (popmax 0.0889%, sas); Associated with atypical hemolytic-uremic syndrome with B factor anomaly.

How common is CFB p.Val516= (c.1548G>A) in the general population?

CFB p.Val516= (c.1548G>A) is ultra-rare (popmax 0.0889%, sas) (gnomAD).

CFB p.Val516=

Q: What condition is associated with CFB p.Val516= (c.1548G>A)?

CFB p.Val516= (c.1548G>A) is associated with atypical hemolytic-uremic syndrome with B factor anomaly, macular degeneration (ClinVar).

c.1548G>A · rs553118090 · VCV905719

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0889%, sas)

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 0.68	GERP -1.5, phastCons 1
Overall
CADD	8.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0889% South Asian · 81/91,084 alleles

Filtering AF 0.0733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0675%

Overall 0.0115% 186/1,613,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0889%	1,124
Admixed American	0.0217%	4,617
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,812
European (non-Finnish)	0.00703%	14,217

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.Val516=
Coding: c.1548G>A
MANE Select: NM_001710
dbSNP: rs553118090
Type: single nucleotide variant
Location: chr6:31950327 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 516: a β-strand; 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

Also linked: macular degeneration

Similar variants

CFB p.Val516Ala 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.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

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-val516 (accessed [today's date]).

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