TTI1 p.Pro1020=
c.3060C>T · VCV4891130
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0573%, afr)
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 4 | GERP 0.46, phastCons 1 |
| Overall | ||
| CADD | 12.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0573%
African / African-American · 43/75,022 alleles
Filtering AF
0.0436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.039%
Overall
0.00613%
99/1,614,040 alleles · ultra-rare
exomes 68/1,461,828 · genomes 31/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0573% | 1,745 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0133% | 7,502 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| East Asian | 0.00446% | 22,439 |
| European (non-Finnish) | 0.00305% | 32,778 |
| South Asian | 0.0011% | 91,074 |
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
- TTI1
- Protein
- p.Pro1020=
- Coding
- c.3060C>T
- MANE Select
- NM_001303457
- Type
- single nucleotide variant
- Location
- chr20:37996401 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38 · 3 PDB
- Residue 1020
- a UniProt-annotated variant site (in nedmim; likely pathogenic)
Similar variants
- TTI1 p.Ala806Thr Uncertain significance ★★ ⚠ same type
- TTI1 p.Arg519Gln Uncertain significance ★★ ⚠ same type
- TTI1 p.Arg724Gly Uncertain significance ★★ ⚠ same type
- TTI1 p.Arg869Cys Uncertain significance ★★ same type
- TTI1 p.Cys86Tyr Uncertain significance ★★ ⚠ same type
- TTI1 p.His229Tyr Uncertain significance ★★ ⚠ same type
- TTI1 p.His513Tyr Uncertain significance ★★ ⚠ same type
- TTI1 p.Ile634Thr Uncertain significance ★★ ⚠ 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/tti1-p-pro1020 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown