TNIK p.Arg438=
c.1312A>C · rs376653606 · VCV743996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, 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 0.21 | GERP -4.2, phastCons 0.99 |
| Overall | ||
| CADD | 1.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,026 alleles
Filtering AF
0.00879%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00823%
Overall
0.00835%
134/1,604,662 alleles · ultra-rare
exomes 131/1,452,582 · genomes 3/152,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,026 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,203 |
| European (non-Finnish) | 0.0103% | 9,716 |
| Admixed American | 0.0034% | 29,384 |
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.Arg438=
- Coding
- c.1312A>C
- MANE Select
- NM_015028
- dbSNP
- rs376653606
- Type
- single nucleotide variant
- Location
- chr3:171140419 (GRCh38)
- Gene constraint
- LOEUF 0.338 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.60 · 12 PDB
- Residue 438
- the 'mediates interaction with nedd4' region; the 'disordered' region
Similar variants
- 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
- TNIK c.1419+19A>G 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/tnik-p-arg438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown