ZCCHC8 p.Phe644=
c.1932T>C · rs755650350 · VCV3005193
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -2.8 | GERP -2.6 |
| Overall | ||
| CADD | 0.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,902 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000867%
14/1,613,866 alleles · very rare
exomes 12/1,461,710 · genomes 2/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,902 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,466 |
| European (non-Finnish) | 0.00102% | 98,325 |
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.Phe644=
- Coding
- c.1932T>C
- MANE Select
- NM_017612
- dbSNP
- rs755650350
- Type
- single nucleotide variant
- Location
- chr12:122473689 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 8 PDB
- Residue 644
- the 'disordered' 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-phe644 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown