VSX2 p.Ala64=
c.192G>A · rs2139628546 · VCV1156698
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00242%, eas)
Conditions
1
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 -0.3 | GERP -2.1, phastCons 0.017 |
| Overall | ||
| CADD | 8.834 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00242%
East Asian · 1/41,300 alleles
Filtering AF
7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000322%
5/1,550,738 alleles · very rare
exomes 5/1,398,430 · genomes 0/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00242% | 41,300 |
| South Asian | 0.00119% | 84,154 |
| European (non-Finnish) | 0.000261% | 382,580 |
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.Ala64=
- Coding
- c.192G>A
- MANE Select
- NM_182894
- dbSNP
- rs2139628546
- Type
- single nucleotide variant
- Location
- chr14:74239753 (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-ala64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown