CFHR4 p.Glu402=
c.1206G>A · rs201709230 · VCV2637649
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0805%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.84 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.76 | gain · loss 0.44 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.48 | GERP 1, phastCons 0.068 |
| Overall | ||
| CADD | 20.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0805%
European (non-Finnish) · 947/1,176,250 alleles
Filtering AF
0.0762%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0745%
Overall
0.0623%
998/1,602,932 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0805% | 1,242 |
| Remaining individualsnot grpmax-eligible | 0.0467% | 2,141 |
| Admixed American | 0.0173% | 5,783 |
| African / African-American | 0.0149% | 6,710 |
| Finnishnot grpmax-eligible | 0.00158% | 63,490 |
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
- CFHR4
- Protein
- p.Glu402=
- Coding
- c.1206G>A
- MANE Select
- NM_001201550
- dbSNP
- rs201709230
- Type
- single nucleotide variant
- Location
- chr1:196914520 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 402
- a disulfide bond; the sushi 7 domain
Similar variants
- CFHR4 p.Glu402Gly Uncertain significance ★ ⚠ same residue
- CFHR4 p.Ala159Val Uncertain significance ★★ ⚠ same type
- CFHR4 p.Arg40His Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ile318Thr Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ser199Tyr Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ser507Leu Uncertain significance ★★ ⚠ same type
- CFHR4 p.Trp68Ter Uncertain significance ★★ same type
- CFHR4 p.Tyr238Ser Uncertain significance ★★ ⚠ 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/cfhr4-p-glu402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown