VSX2 p.Pro250=
c.750G>A · rs192712847 · VCV314196
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.957%, eas)
Conditions
3
microphthalmia, isolated, with coloboma 3
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 -5.2 | GERP -4.8 |
| Overall | ||
| CADD | 5.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.957%
East Asian · 428/44,720 alleles
Filtering AF
0.882%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.853%
Overall
0.03%
484/1,611,842 alleles · rare
exomes 432/1,461,034 · genomes 52/150,808 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.957% | 104 |
| South Asian | 0.0297% | 3,365 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,672 |
| Admixed American | 0.00837% | 11,954 |
| African / African-American | 0.00134% | 74,448 |
| European (non-Finnish) | 0.000509% | 196,553 |
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.Pro250=
- Coding
- c.750G>A
- MANE Select
- NM_182894
- dbSNP
- rs192712847
- Type
- single nucleotide variant
- Location
- chr14:74259772 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.65
- Residue 250
- the cvc domain
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-pro250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown