TTK p.Thr423=
c.1269C>G · rs139578466 · VCV775239
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.29%, mid)
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 0.001 | GERP -0.8 |
| Overall | ||
| CADD | 6.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.29%
Middle Eastern · 78/6,036 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.976%
Overall
0.0644%
1,037/1,611,010 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.29% | 77 |
| Admixed American | 0.154% | 648 |
| Remaining individualsnot grpmax-eligible | 0.144% | 693 |
| South Asian | 0.0863% | 1,159 |
| European (non-Finnish) | 0.0561% | 1,783 |
| African / African-American | 0.0361% | 2,772 |
| Finnishnot grpmax-eligible | 0.0125% | 7,990 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0102% | 9,843 |
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
- TTK
- Protein
- p.Thr423=
- Coding
- c.1269C>G
- MANE Select
- NM_003318
- dbSNP
- rs139578466
- Type
- single nucleotide variant
- Location
- chr6:80026389 (GRCh38)
- Gene constraint
- LOEUF 0.666 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.11 · 78 PDB
Similar variants
- TTK p.Ala110Pro Uncertain significance ★ ⚠ same type
- TTK p.Ala251Gly Uncertain significance ★ ⚠ same type
- TTK p.Ala401Pro Uncertain significance ★ ⚠ same type
- TTK p.Ala402Val Uncertain significance ★ ⚠ same type
- TTK p.Ala787Gly Uncertain significance ★ ⚠ same type
- TTK p.Arg129Cys Uncertain significance ★ ⚠ same type
- TTK p.Arg256Pro Uncertain significance ★ ⚠ same type
- TTK p.Arg414Gly 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/ttk-p-thr423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown