TNIK p.Arg424=
c.1272C>T · rs376964973 · VCV2654276
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, 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 -0.72 | GERP -4.2 |
| Overall | ||
| CADD | 6.037 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
Middle Eastern · 4/6,080 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.00118%
19/1,612,758 alleles · ultra-rare
exomes 16/1,460,638 · genomes 3/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0658% | 1,520 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,209 |
| South Asian | 0.0022% | 45,499 |
| European (non-Finnish) | 0.000933% | 107,224 |
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
- TNIK
- Protein
- p.Arg424=
- Coding
- c.1272C>T
- MANE Select
- NM_015028
- dbSNP
- rs376964973
- Type
- single nucleotide variant
- Location
- chr3:171140459 (GRCh38)
- Gene constraint
- LOEUF 0.338 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.60 · 12 PDB
- Residue 424
- the 'mediates interaction with nedd4' region; the 'disordered' region
Similar variants
- TNIK p.Arg424Cys Uncertain significance ★ ⚠ same residue
- TNIK p.Arg545Trp Uncertain significance ★★ ⚠ same type
- TNIK p.Arg632Cys Uncertain significance ★★ ⚠ same type
- TNIK p.Arg914Gln Uncertain significance ★★ ⚠ same type
- TNIK p.Asn1353Ser Uncertain significance ★★ ⚠ same type
- TNIK p.Gly910Glu Uncertain significance ★★ ⚠ same type
- TNIK p.Ile653Phe Uncertain significance ★★ ⚠ same type
- TNIK p.Lys913Gln 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/tnik-p-arg424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown