TTI2 p.Leu373=
c.1117T>C · rs778746953 · VCV2658531
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0089%, nfe)
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 0.49 | GERP -3.8, phastCons 0.29 |
| Overall | ||
| CADD | 10.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0089%
European (non-Finnish) · 105/1,180,042 alleles
Filtering AF
0.00749%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.007%
Overall
0.00657%
106/1,613,776 alleles · very rare
exomes 102/1,461,700 · genomes 4/152,076 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0089% | 11,238 |
| South Asian | 0.0011% | 91,084 |
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.Leu373=
- Coding
- c.1117T>C
- MANE Select
- NM_001102401
- dbSNP
- rs778746953
- Type
- single nucleotide variant
- Location
- chr8:33503571 (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-leu373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown