ZIC2 p.Pro64=
c.192G>C · rs1482991117 · VCV2898948
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000176%, nfe)
Conditions
1
holoprosencephaly 5
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 -4.4 | GERP -3.7 |
| Overall | ||
| CADD | 9.079 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000176%
European (non-Finnish) · 2/1,133,982 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000133%
2/1,507,494 alleles · very rare
exomes 2/1,355,912 · genomes 0/151,582 · 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
- ZIC2
- Protein
- p.Pro64=
- Coding
- c.192G>C
- MANE Select
- NM_007129
- dbSNP
- rs1482991117
- Type
- single nucleotide variant
- Location
- chr13:99982256 (GRCh38)
- Gene constraint
- LOEUF 0.52 · pLI 0.96 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.36
Similar variants
- ZIC2 p.Pro64Ser Uncertain significance ★ ⚠ same residue
- ZIC2 p.Ala228Gly Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Ala26Gly Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Arg180Cys Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Arg346Leu Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Glu305Val Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Gly155Ser Uncertain significance ★★ ⚠ same condition
- ZIC2 p.Gly478Arg Uncertain significance ★★ ⚠ same condition
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/zic2-p-pro64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown