Is CFH p.Ser1069= (c.3207T>C) pathogenic?

CFH p.Ser1069= (c.3207T>C) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-22). Rare (popmax 0.606%, afr); Associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II.

What condition is associated with CFH p.Ser1069= (c.3207T>C)?

CFH p.Ser1069= (c.3207T>C) is associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Ser1069= (c.3207T>C) in the general population?

CFH p.Ser1069= (c.3207T>C) is rare (popmax 0.606%, afr) (gnomAD).

CFH p.Ser1069=

c.3207T>C · rs62641697 · VCV294523

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.606%, afr)

Conditions

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II

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 1.7
Overall
CADD	3.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.606% African / African-American · 455/75,044 alleles

Filtering AF 0.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.542%

Overall 0.067% 1,082/1,614,012 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.25%	80
African / African-Americangrpmax	0.606%	165
Remaining individualsnot grpmax-eligible	0.19%	525
Middle Eastern	0.132%	757
Admixed American	0.0583%	1,715
South Asian	0.0154%	6,506
European (non-Finnish)	0.00695%	14,389

Ashkenazi Jewish 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: CFH
Protein: p.Ser1069=
Coding: c.3207T>C
MANE Select: NM_000186
dbSNP: rs62641697
Type: single nucleotide variant
Location: chr1:196743525 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1069: the sushi 18 domain; a disulfide bond

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

Disease context

Also linked: basal laminar drusen hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency age related macular degeneration 4 atypical hemolytic-uremic syndrome

Similar variants

CFH p.Ser1069Pro Likely benign ★ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/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.Arg1215Leu 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-ser1069 (accessed [today's date]).

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