CFHR4 p.Arg412=
c.1234C>A · rs75774768 · VCV782977
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.267%, 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 -1.2 | GERP -2.4 |
| Overall | ||
| CADD | 0.739 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.267%
European (non-Finnish) · 3,144/1,177,702 alleles
Filtering AF
0.259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.256%
Overall
0.209%
3,364/1,608,632 alleles · rare
exomes 3,151/1,457,404 · genomes 213/151,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.267% | 375 |
| Remaining individualsnot grpmax-eligible | 0.151% | 662 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0678% | 1,474 |
| African / African-American | 0.0566% | 1,766 |
| Finnishnot grpmax-eligible | 0.0551% | 1,816 |
| Admixed American | 0.0437% | 2,288 |
| South Asian | 0.00332% | 30,141 |
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.Arg412=
- Coding
- c.1234C>A
- MANE Select
- NM_001201550
- dbSNP
- rs75774768
- Type
- single nucleotide variant
- Location
- chr1:196914548 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 412
- the sushi 7 domain
Similar variants
- CFHR4 p.Arg412Trp Benign/Likely benign ★★ same residue
- CFHR4 p.Arg412Gln Conflicting classifications of pathogenicity ★ ⚠ 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
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-arg412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown