PREP p.His680=
c.2040C>T · rs116581811 · VCV784094
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.04%, 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 -2.7 | GERP -4.9 |
| Overall | ||
| CADD | 5.775 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.04%
African / African-American · 1,533/75,050 alleles
Filtering AF
1.96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.92%
Overall
0.106%
1,708/1,614,208 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.04% | 49 |
| Middle Eastern | 0.149% | 673 |
| Remaining individualsnot grpmax-eligible | 0.107% | 933 |
| Admixed American | 0.0966% | 1,035 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| European (non-Finnish) | 0.00322% | 31,054 |
| East Asian | 0.00223% | 44,874 |
| South Asian | 0.0011% | 91,084 |
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
- PREP
- Protein
- p.His680=
- Coding
- c.2040C>T
- MANE Select
- NM_014889 · reported on NM_002726
- dbSNP
- rs116581811
- Type
- single nucleotide variant
- Location
- chr6:105278237 (GRCh38)
- Structure
- AlphaFold pLDDT 94.44 · 8 PDB
- Residue 680
- an α-helix
Similar variants
- PITRM1 p.Met680Leu Uncertain significance ★ ⚠ same residue
- PITRM1 p.Thr931Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- PITRM1 p.Ala1003Thr Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala559Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala887Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala942Val Uncertain significance ★★ ⚠ same type
- PITRM1 p.Ala965Thr Uncertain significance ★★ ⚠ same type
- PITRM1 p.Arg32Trp 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/prep-p-his680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown