CFHR4 p.Thr380=
c.1140A>G · VCV4683999
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -12 | GERP -3.5 |
| Overall | ||
| CADD | 0.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,876 alleles
Filtering AF
0.00544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00105%
17/1,611,640 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,554 |
| South Asian | 0.0011% | 90,890 |
| European (non-Finnish) | 0.000763% | 130,993 |
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.Thr380=
- Coding
- c.1140A>G
- MANE Select
- NM_001201550
- Type
- single nucleotide variant
- Location
- chr1:196912882 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 380
- a disulfide bond; 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-thr380 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown