TANC2 p.Ser1908=
c.5724G>A · VCV4083892
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, 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 -1.8 | GERP -5.9 |
| Overall | ||
| CADD | 1.663 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.0018%
29/1,613,806 alleles · ultra-rare
exomes 25/1,461,690 · genomes 4/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| South Asian | 0.00878% | 11,386 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,234 |
| East Asian | 0.00223% | 44,894 |
| Finnishnot grpmax-eligible | 0.00156% | 63,976 |
| European (non-Finnish) | 0.00127% | 78,660 |
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
- TANC2
- Protein
- p.Ser1908=
- Coding
- c.5724G>A
- MANE Select
- NM_001394998
- Type
- single nucleotide variant
- Location
- chr17:63421454 (GRCh38)
- Gene constraint
- LOEUF 0.17 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.92
- Residue 1908
- a UniProt-annotated variant site (in iddalds; strongly reduced interaction with kif1a; strongly reduced localization at the dendritic spine); a UniProt-annotated variant site (in iddalds)
Similar variants
- TANC2 p.Arg1516Gln Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg1741Gln Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg1923Ter Uncertain significance ★★ same type
- TANC2 p.Arg268Cys Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg388His Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg466Lys Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg563Trp Uncertain significance ★★ ⚠ same type
- TANC2 p.Arg834Cys 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/tanc2-p-ser1908 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown