CFHR1 p.Pro223=
c.669G>A · rs12406079 · VCV1242693
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 19%, mid) — too common for a highly-penetrant pathogenic allele
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 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.7 |
| Overall | ||
| CADD | 2.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19%
Middle Eastern · 1,017/5,348 alleles
Filtering AF
18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.7%
Overall
13.7%
208,252/1,524,348 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 19% | 5 |
| European (non-Finnish) | 14.9% | 7 |
| Remaining individualsnot grpmax-eligible | 13.7% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 13.3% | 8 |
| Admixed American | 11.6% | 9 |
| East Asian | 10.9% | 9 |
| South Asian | 7.99% | 13 |
| Finnishnot grpmax-eligible | 7.64% | 13 |
| African / African-American | 7.29% | 14 |
| Amishnot grpmax-eligible | 2.93% | 34 |
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
- CFHR1
- Protein
- p.Pro223=
- Coding
- c.669G>A
- MANE Select
- NM_002113
- dbSNP
- rs12406079
- Type
- single nucleotide variant
- Location
- chr1:196830561 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.21 · 2 PDB
- Residue 223
- a disulfide bond; the sushi 4 domain
Similar variants
- CFHR1 p.Pro223Leu Uncertain significance ★★ ⚠ same residue
- CFHR1 p.Asp218Asn Uncertain significance ★★ ⚠ same type
- CFHR1 p.Gln44Ter Uncertain significance ★★ same type
- CFHR1 p.Ile214Asn Uncertain significance ★★ ⚠ same type
- CFHR1 p.Ile70Val Uncertain significance ★★ ⚠ same type
- CFHR1 p.Tyr304Cys Uncertain significance ★★ ⚠ same type
- CFHR1 c.253+108G>C Benign ★★ same type
- CFHR1 c.253+213G>A Benign ★★ 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/cfhr1-p-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown