TNC p.Gln500=
c.1500A>G · VCV4904311
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.9 | |
| Overall | ||
| CADD | 0.098 | 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
0.0107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.01%
Overall
0.0112%
180/1,614,064 alleles · ultra-rare
exomes 166/1,461,858 · genomes 14/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| African / African-American | 0.0174% | 5,764 |
| South Asian | 0.0154% | 6,507 |
| European (non-Finnish) | 0.0124% | 8,083 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| East Asian | 0.00223% | 44,896 |
| Admixed American | 0.00167% | 60,004 |
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
- TNC
- Protein
- p.Gln500=
- Coding
- c.1500A>G
- MANE Select
- NM_002160
- Type
- single nucleotide variant
- Location
- chr9:115086231 (GRCh38)
- Gene constraint
- LOEUF 0.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.48 · 21 PDB
- Residue 500
- the egf-like 12 domain
Similar variants
- TNC p.Arg1127Trp Uncertain significance ★★ ⚠ same type
- TNC p.Arg608Cys Uncertain significance ★★ ⚠ same type
- TNC p.Arg669His Uncertain significance ★★ ⚠ same type
- TNC p.Arg747Trp Uncertain significance ★★ ⚠ same type
- TNC p.Asn507Lys Uncertain significance ★★ ⚠ same type
- TNC p.Asp2059Glu Uncertain significance ★★ ⚠ same type
- TNC p.Asp831Asn Uncertain significance ★★ ⚠ same type
- TNC p.Asp971Asn 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/tnc-p-gln500 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown