VSX2 p.Ser22=
c.66G>C · rs542328201 · VCV468360
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, afr)
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 2.1 | GERP 0.22, phastCons 1 |
| Overall | ||
| CADD | 10.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
African / African-American · 37/73,168 alleles
Filtering AF
0.0377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0332%
Overall
0.00367%
57/1,551,140 alleles · ultra-rare
exomes 34/1,398,834 · genomes 23/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0506% | 1,978 |
| South Asian | 0.0155% | 6,466 |
| Admixed American | 0.00588% | 17,002 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,035 |
| East Asian | 0.00244% | 40,912 |
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.Ser22=
- Coding
- c.66G>C
- MANE Select
- NM_182894
- dbSNP
- rs542328201
- Type
- single nucleotide variant
- Location
- chr14:74239627 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.65
- Residue 22
- 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-ser22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown