TKT p.Asp424=
c.1272C>T · rs148178844 · VCV762214
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 -4.4 | GERP -5.5 |
| Overall | ||
| CADD | 2.142 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/75,038 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00378%
61/1,614,180 alleles · ultra-rare
exomes 51/1,461,868 · genomes 10/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,338 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| East Asian | 0.00446% | 22,438 |
| European (non-Finnish) | 0.0039% | 25,653 |
| South Asian | 0.0011% | 91,090 |
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
- TKT
- Protein
- p.Asp424=
- Coding
- c.1272C>T
- MANE Select
- NM_001064
- dbSNP
- rs148178844
- Type
- single nucleotide variant
- Location
- chr3:53229130 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.11 · 13 PDB
Similar variants
- TKT p.Arg591Trp Uncertain significance ★★ ⚠ same type
- TKT p.Asp106Tyr Uncertain significance ★★ ⚠ same type
- TKT p.Leu153Pro Uncertain significance ★★ ⚠ same type
- TKT p.Leu98Pro Uncertain significance ★★ ⚠ same type
- TKT p.Tyr202Cys Uncertain significance ★★ same type
- TKT c.1264+17T>C Benign ★★ same type
- TKT c.1265-47G>C Benign ★★ same type
- TKT c.1697-49C>T Benign ★★ 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/tkt-p-asp424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown