Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 96.7%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
exudative vitreoretinopathy 5
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 0.78 | GERP -5.2, phastCons 0.96 |
| Overall | ||
| CADD | 1.555 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
96.7%
East Asian · 43,394/44,866 alleles
Filtering AF
96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 95.6%
Overall
76.7%
1,238,104/1,613,870 alleles · common
exomes 1,119,499/1,461,816 · genomes 118,605/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 96.7% | 1 |
| South Asian | 90.3% | 1 |
| Middle Eastern | 88.3% | 1 |
| Admixed American | 84% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 81.6% | 1 |
| Amishnot grpmax-eligible | 80.8% | 1 |
| Remaining individualsnot grpmax-eligible | 78.5% | 1 |
| African / African-American | 78.5% | 1 |
| European (non-Finnish) | 74.7% | 1 |
| Finnishnot grpmax-eligible | 67.2% | 1 |
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
- TSPAN12
- Protein
- p.Pro255=
- Coding
- c.765G>T
- MANE Select
- NM_012338
- dbSNP
- rs41623
- Type
- single nucleotide variant
- Location
- chr7:120788745 (GRCh38)
- Gene constraint
- LOEUF 0.655 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 1 PDB
Similar variants
- TSPAN12 p.Pro255Ala Uncertain significance ★ ⚠ same residue
- TSPAN12 c.67-2A>G Likely pathogenic ★★ same condition
- TSPAN12 p.Cys181Phe Pathogenic ★★ same condition
- TSPAN12 p.Cys189Tyr Pathogenic/Likely pathogenic ★★ same condition
- TSPAN12 p.Leu101His Likely pathogenic ★★ same condition
- TSPAN12 p.Tyr138Cys Pathogenic/Likely pathogenic ★★ same condition
- TSPAN12 c.-102G>A Uncertain significance ★★ same condition
- TSPAN12 p.Arg11His Uncertain significance ★★ ⚠ 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/tspan12-p-pro255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown