CFB p.His451=
c.1353T>C · rs375168705 · VCV1624069
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.421 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.8 | GERP -4 |
| Overall | ||
| CADD | 1.569 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/74,918 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00552%
89/1,613,720 alleles · ultra-rare
exomes 80/1,461,534 · genomes 9/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,492 |
| European (non-Finnish) | 0.00644% | 15,527 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
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
- CFB
- Protein
- p.His451=
- Coding
- c.1353T>C
- MANE Select
- NM_001710
- dbSNP
- rs375168705
- Type
- single nucleotide variant
- Location
- chr6:31949502 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.54 · 28 PDB
- Residue 451
- the vwfa domain
Similar variants
- CFB c.2140-1G>C Uncertain significance ★★ same type
- CFB c.-3G>A Uncertain significance ★★ same type
- CFB p.Ala162Val Uncertain significance ★★ ⚠ same type
- CFB p.Ala289Val Uncertain significance ★★ same type
- CFB p.Ala567Gly Uncertain significance ★★ ⚠ same type
- CFB p.Arg117Trp Uncertain significance ★★ ⚠ same type
- CFB p.Arg138Gln Uncertain significance ★★ ⚠ same type
- CFB p.Arg138Trp 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/cfb-p-his451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown