CFHR4 p.Lys394=
c.1182A>G · VCV4684003
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.542%, afr)
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 -2.6 | GERP 0.57 |
| Overall | ||
| CADD | 0.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.542%
African / African-American · 401/74,018 alleles
Filtering AF
0.498%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.481%
Overall
0.029%
466/1,605,092 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.542% | 185 |
| Admixed American | 0.0664% | 1,507 |
| Remaining individualsnot grpmax-eligible | 0.037% | 2,700 |
| South Asian | 0.00335% | 29,868 |
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.Lys394=
- Coding
- c.1182A>G
- MANE Select
- NM_001201550
- Type
- single nucleotide variant
- Location
- chr1:196914496 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 394
- the sushi 6 domain
Similar variants
- 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
- CFHR4 c.1180+4A>C Benign/Likely benign ★★ 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-lys394 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown