ZCCHC8 p.Pro482=
c.1446C>T · rs74736991 · VCV1604337
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.657%, 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 -0.17 | GERP -2.2 |
| Overall | ||
| CADD | 5.254 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.657%
African / African-American · 468/71,246 alleles
Filtering AF
0.608%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.588%
Overall
0.0346%
524/1,514,372 alleles · rare
exomes 239/1,362,150 · genomes 285/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.657% | 152 |
| Admixed American | 0.0441% | 2,266 |
| Remaining individualsnot grpmax-eligible | 0.0275% | 3,631 |
| Middle Eastern | 0.0179% | 5,598 |
| South Asian | 0.00981% | 10,196 |
| Finnishnot grpmax-eligible | 0.00165% | 60,490 |
| European (non-Finnish) | 0.00114% | 87,663 |
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.Pro482=
- Coding
- c.1446C>T
- MANE Select
- NM_017612
- dbSNP
- rs74736991
- Type
- single nucleotide variant
- Location
- chr12:122474175 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 8 PDB
- Residue 482
- the 'disordered' region
Similar variants
- ZCCHC8 p.Pro482Arg 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-pro482 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown