ZCCHC8 p.Pro489=
c.1467A>G · rs376747026 · VCV1638015
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0211%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 7.546 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0211%
African / African-American · 15/71,144 alleles
Filtering AF
0.0129%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0105%
Overall
0.000993%
15/1,511,030 alleles · ultra-rare
exomes 4/1,359,060 · genomes 11/151,970 · joint denominator
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
- ZCCHC8
- Protein
- p.Pro489=
- Coding
- c.1467A>G
- MANE Select
- NM_017612
- dbSNP
- rs376747026
- Type
- single nucleotide variant
- Location
- chr12:122474154 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 8 PDB
- Residue 489
- the 'disordered' region
Similar variants
- ZCCHC8 p.Pro489Arg Uncertain significance ★ same residue
- ZCCHC8 p.Ala392Ser Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala409Glu Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala409Val Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala442Val Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala47Ser Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala514Thr Uncertain significance ★★ ⚠ same type
- ZCCHC8 p.Ala667Val 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/zcchc8-p-pro489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown