TTI1 p.Ser668=
c.2004T>C · VCV4822664
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000932%, 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 2.8 | GERP -0.33, phastCons 1 |
| Overall | ||
| CADD | 7.787 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000932%
European (non-Finnish) · 11/1,180,042 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000681%
11/1,614,126 alleles · very rare
exomes 9/1,461,888 · genomes 2/152,238 · joint denominator
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.Ser668=
- Coding
- c.2004T>C
- MANE Select
- NM_001303457
- Type
- single nucleotide variant
- Location
- chr20:38011813 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38 · 3 PDB
- Residue 668
- 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-ser668 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown