CFH p.Ala425=
c.1275G>A · rs545227407 · VCV2179841
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0669%, eas)
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 -0.94 | GERP -3.8 |
| Overall | ||
| CADD | 1.151 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0669%
East Asian · 30/44,812 alleles
Filtering AF
0.0482%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0418%
Overall
0.00434%
70/1,613,360 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0669% | 1,494 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,492 |
| South Asian | 0.00549% | 18,216 |
| Admixed American | 0.00501% | 19,953 |
| European (non-Finnish) | 0.0022% | 45,371 |
| African / African-American | 0.00133% | 74,970 |
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.Ala425=
- Coding
- c.1275G>A
- MANE Select
- NM_000186
- dbSNP
- rs545227407
- Type
- single nucleotide variant
- Location
- chr1:196690178 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 425
- an α-helix; a disulfide bond; the sushi 7 domain
Similar variants
- CFH p.Ala425Val 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-ala425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown