CFH p.Val686=
c.2058G>A · rs541280297 · VCV2416344
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0725%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.44 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.31 | gain · loss 0.17 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.2 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 17.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0725%
South Asian · 66/91,064 alleles
Filtering AF
0.0584%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0533%
Overall
0.00452%
73/1,613,636 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0725% | 1,380 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| European (non-Finnish) | 8.48e-05% | 1,179,697 |
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.Val686=
- Coding
- c.2058G>A
- MANE Select
- NM_000186
- dbSNP
- rs541280297
- Type
- single nucleotide variant
- Location
- chr1:196726762 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 686
- the sushi 11 domain; a β-strand
Similar variants
- CFH p.Val686Ala Uncertain significance ★ ⚠ same residue
- CFH p.Val686Met 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
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-val686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown