ZCCHC8 p.Pro696=
c.2088C>T · rs756356363 · VCV3012843
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 0.51 | GERP -0.94, phastCons 0.99 |
| Overall | ||
| CADD | 7.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,014 alleles
Overall
6.2e-05%
1/1,613,864 alleles · very rare
exomes 1/1,461,626 · genomes 0/152,238 · 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.Pro696=
- Coding
- c.2088C>T
- MANE Select
- NM_017612
- dbSNP
- rs756356363
- Type
- single nucleotide variant
- Location
- chr12:122473533 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 8 PDB
- Residue 696
- an α-helix; the 'mtrex binding' region
Similar variants
- 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
- ZCCHC8 p.Arg312Gln 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-pro696 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown