Is CFH p.Cys569= (c.1707C>T) pathogenic?

CFH p.Cys569= (c.1707C>T) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Rare (popmax 0.398%, afr); Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Cys569= (c.1707C>T)?

CFH p.Cys569= (c.1707C>T) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1, basal laminar drusen, complement factor H deficiency (ClinVar).

How common is CFH p.Cys569= (c.1707C>T) in the general population?

CFH p.Cys569= (c.1707C>T) is rare (popmax 0.398%, afr) (gnomAD).

CFH p.Cys569=

c.1707C>T · rs144976181 · VCV722920

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.398%, afr)

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

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>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.7	GERP -1.7
Overall
CADD	4.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.398% African / African-American · 298/74,944 alleles

Filtering AF 0.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.346%

Overall 0.0257% 414/1,612,442 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.398%	251
Middle Eastern	0.0992%	1,008
Remaining individualsnot grpmax-eligible	0.04%	2,497
Admixed American	0.0367%	2,726
East Asian	0.0291%	3,442
Finnishnot grpmax-eligible	0.00626%	15,975
European (non-Finnish)	0.00373%	26,794
South Asian	0.0022%	45,488

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: CFH
Protein: p.Cys569=
Coding: c.1707C>T
MANE Select: NM_000186
dbSNP: rs144976181
Type: single nucleotide variant
Location: chr1:196725131 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 569: the sushi 10 domain; a disulfide bond

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

Disease context

hemolytic uremic syndrome, atypical, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal laminar drusen complement factor H deficiency age related macular degeneration 4

Similar variants

CFH p.Cys569Ter Pathogenic ★★ same residue
CFH p.Cys569Arg Uncertain significance ★ ⚠ same residue
CFH p.Cys569Tyr Uncertain significance ★ ⚠ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ 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/cfh-p-cys569 (accessed [today's date]).

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