VSX2 p.Ala264=
c.792C>T · rs769079054 · VCV1105011
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00448%, sas)
Conditions
1
isolated microphthalmia 2
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 -7.1 | GERP -4 |
| Overall | ||
| CADD | 2.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00448%
South Asian · 4/89,354 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000904%
Overall
0.000498%
8/1,606,716 alleles · very rare
exomes 7/1,454,476 · genomes 1/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00448% | 22,338 |
| European (non-Finnish) | 0.00034% | 294,312 |
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.Ala264=
- Coding
- c.792C>T
- MANE Select
- NM_182894
- dbSNP
- rs769079054
- Type
- single nucleotide variant
- Location
- chr14:74260625 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.65
- Residue 264
- the 'disordered' region
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-ala264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown