VSX2 p.Ala63=
c.189G>T · rs1205909190 · VCV1596807
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00485%, eas)
Conditions
2
isolated microphthalmia 2
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 -4.6 | GERP -4 |
| Overall | ||
| CADD | 0.956 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00485%
East Asian · 2/41,256 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00044%
Overall
0.000903%
14/1,550,178 alleles · very rare
exomes 13/1,398,010 · genomes 1/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00485% | 20,628 |
| European (non-Finnish) | 0.00105% | 95,624 |
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
- VSX2
- Protein
- p.Ala63=
- Coding
- c.189G>T
- MANE Select
- NM_182894
- dbSNP
- rs1205909190
- Type
- single nucleotide variant
- Location
- chr14:74239750 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.65
Similar variants
- VSX2 c.371-1G>A Pathogenic ★★ same condition
- VSX2 p.Arg200Gln Pathogenic ★★ same condition
- VSX2 p.Arg200Pro Pathogenic/Likely pathogenic ★★ same condition
- VSX2 p.Arg200Ter Pathogenic ★★ same condition
- VSX2 p.Arg227Trp Pathogenic/Likely pathogenic ★★ same condition
- VSX2 p.Cys29Ter Pathogenic/Likely pathogenic ★★ same condition
- VSX2 p.Gln197Ter Pathogenic/Likely pathogenic ★★ same condition
- VSX2 p.Trp195Ter Pathogenic/Likely pathogenic ★★ 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/vsx2-p-ala63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown