CFH p.Ala73=
c.219T>C · rs776075595 · VCV2170701
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00381%, nfe)
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 -0.65 | GERP -3.7 |
| Overall | ||
| CADD | 2.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00381%
European (non-Finnish) · 45/1,179,634 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.00285%
46/1,613,462 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00381% | 26,214 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,456 |
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.Ala73=
- Coding
- c.219T>C
- MANE Select
- NM_000186
- dbSNP
- rs776075595
- Type
- single nucleotide variant
- Location
- chr1:196673138 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 73
- a β-strand; the sushi 1 domain; a disulfide bond
Similar variants
- CFH p.Ala73Val 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-ala73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown