CFH p.Ser209=
c.627A>T · VCV3613144
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00168%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.52 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.33 | GERP -2.2 |
| Overall | ||
| CADD | 16.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00168%
Admixed American · 1/59,686 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.00025%
4/1,601,790 alleles · very rare
exomes 3/1,449,802 · genomes 1/151,988 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00168% | 59,686 |
| European (non-Finnish) | 0.000256% | 390,153 |
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.Ser209=
- Coding
- c.627A>T
- MANE Select
- NM_000186
- Type
- single nucleotide variant
- Location
- chr1:196679630 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 209
- the sushi 4 domain
Similar variants
- CFH p.Ser209Leu Uncertain significance ★★ ⚠ same residue
- CFH c.1337-2A>G Likely pathogenic ★★ same type
- CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same type
- CFH c.2236+1G>C Likely pathogenic ★★ same type
- CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same type
- CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same type
- CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same type
- CFH p.Arg1215Leu Likely pathogenic ★★ same type
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-ser209 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown