CFH p.Ala1010=
c.3030G>A · rs1290292015 · VCV1900407
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.29 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.56 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.69 | GERP -3.7, phastCons 0.94 |
| Overall | ||
| CADD | 9.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000929%
15/1,614,130 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.00102% | 98,332 |
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.Ala1010=
- Coding
- c.3030G>A
- MANE Select
- NM_000186
- dbSNP
- rs1290292015
- Type
- single nucleotide variant
- Location
- chr1:196741948 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 1010
- a UniProt-annotated variant site (in); the sushi 17 domain; a disulfide bond
Similar variants
- CFH p.Ala1010Thr Uncertain significance ★★ ⚠ same residue
- CFH p.Ala1010Val Conflicting classifications of pathogenicity ★ ⚠ 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
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-ala1010 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown