ZCCHC8 p.Pro616=
c.1848G>A · rs532006067 · VCV761516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, 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 -2.1 | GERP -3 |
| Overall | ||
| CADD | 4.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,986 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00161%
26/1,613,148 alleles · ultra-rare
exomes 10/1,460,904 · genomes 16/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,571 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
| South Asian | 0.0022% | 45,522 |
| European (non-Finnish) | 8.48e-05% | 1,179,276 |
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.Pro616=
- Coding
- c.1848G>A
- MANE Select
- NM_017612
- dbSNP
- rs532006067
- Type
- single nucleotide variant
- Location
- chr12:122473773 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 8 PDB
Similar variants
- ZCCHC8 p.Pro616Leu Likely benign ★ 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-pro616 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown