ZIC2 p.Pro438=
c.1314G>A · rs762579383 · VCV767479
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -1.4 | GERP -3.3 |
| Overall | ||
| CADD | 5.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,894 alleles
Filtering AF
0.000804%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00106%
17/1,596,492 alleles · very rare
exomes 16/1,444,592 · genomes 1/151,900 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,894 |
| European (non-Finnish) | 0.00136% | 73,669 |
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.Pro438=
- Coding
- c.1314G>A
- MANE Select
- NM_007129
- dbSNP
- rs762579383
- Type
- single nucleotide variant
- Location
- chr13:99985397 (GRCh38)
- Gene constraint
- LOEUF 0.52 · pLI 0.96 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.36
- Residue 438
- the 'disordered' region
Similar variants
- 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
- ZIC2 p.Gly481Val 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-pro438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown