TTI2 p.Pro250=
c.750C>T · rs138257989 · VCV2658533
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.084%, afr)
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 -0.59 | GERP -3.3, phastCons 0.001 |
| Overall | ||
| CADD | 8.836 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.084%
African / African-American · 63/74,968 alleles
Filtering AF
0.0674%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0613%
Overall
0.0096%
155/1,613,958 alleles · ultra-rare
exomes 112/1,461,840 · genomes 43/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.084% | 1,190 |
| Middle Eastern | 0.033% | 3,031 |
| Admixed American | 0.0217% | 4,613 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| European (non-Finnish) | 0.00542% | 18,437 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| East Asian | 0.00223% | 44,872 |
| South Asian | 0.0011% | 91,078 |
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
- TTI2
- Protein
- p.Pro250=
- Coding
- c.750C>T
- MANE Select
- NM_001102401
- dbSNP
- rs138257989
- Type
- single nucleotide variant
- Location
- chr8:33509830 (GRCh38)
- Gene constraint
- LOEUF 0.758 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.85 · 2 PDB
Similar variants
- TTI2 p.Arg334Gln Uncertain significance ★★ ⚠ same type
- TTI2 p.Arg355His Uncertain significance ★★ ⚠ same type
- TTI2 p.Arg379Trp Uncertain significance ★★ ⚠ same type
- TTI2 p.Gly190Val Uncertain significance ★★ ⚠ same type
- TTI2 p.Pro149Leu Uncertain significance ★★ ⚠ same type
- TTI2 p.Thr232Ile Uncertain significance ★★ ⚠ same type
- TTI2 p.Thr237Ala Uncertain significance ★★ ⚠ same type
- TTI2 c.-99-31C>T Benign ★★ same type
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/tti2-p-pro250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown