TANC2 p.Pro1850=
c.5550G>A · VCV4534474
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 -0.88 | GERP -5.5 |
| Overall | ||
| CADD | 0.513 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,004 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00192%
31/1,613,850 alleles · ultra-rare
exomes 28/1,461,710 · genomes 3/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,616 |
| South Asian | 0.0143% | 7,006 |
| East Asian | 0.00223% | 44,900 |
| African / African-American | 0.00134% | 74,900 |
| European (non-Finnish) | 0.000254% | 393,297 |
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.Pro1850=
- Coding
- c.5550G>A
- MANE Select
- NM_001394998
- Type
- single nucleotide variant
- Location
- chr17:63421280 (GRCh38)
- Gene constraint
- LOEUF 0.17 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.92
- Residue 1850
- 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.Pro1850Leu Likely benign ★ same residue
- 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
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-pro1850 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown