TTI1 p.Ser1071=
c.3213C>T · VCV4281425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, 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 -6.6 | GERP -4.7 |
| Overall | ||
| CADD | 0.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,838 alleles
Filtering AF
0.000444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000559%
9/1,611,312 alleles · very rare
exomes 9/1,459,500 · genomes 0/151,812 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,419 |
| East Asian | 0.00224% | 44,736 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,432 |
| European (non-Finnish) | 0.000424% | 235,903 |
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.Ser1071=
- Coding
- c.3213C>T
- MANE Select
- NM_001303457
- Type
- single nucleotide variant
- Location
- chr20:37983513 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38 · 3 PDB
- Residue 1071
- 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-ser1071 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown