TTI1 p.Gln567=
c.1701A>G · rs2515459511 · VCV2652311
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -0.18 | GERP -2.5, phastCons 0.65 |
| Overall | ||
| CADD | 3.815 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Overall
0.000124%
2/1,614,222 alleles · ultra-rare
exomes 2/1,461,894 · genomes 0/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| South Asian | 0.0011% | 91,076 |
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.Gln567=
- Coding
- c.1701A>G
- MANE Select
- NM_001303457
- dbSNP
- rs2515459511
- Type
- single nucleotide variant
- Location
- chr20:38012116 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38 · 3 PDB
- Residue 567
- 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-gln567 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown