TNC p.Thr675=
c.2025G>A · VCV4904301
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0913%, nfe)
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 -15 | |
| Overall | ||
| CADD | 2.711 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0913%
European (non-Finnish) · 1,077/1,180,022 alleles
Filtering AF
0.0867%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0849%
Overall
0.0703%
1,135/1,614,160 alleles · ultra-rare
exomes 1,082/1,461,882 · genomes 53/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0913% | 1,096 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,084 |
| Admixed American | 0.0233% | 4,288 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.00933% | 10,721 |
| East Asian | 0.00892% | 11,216 |
| Finnishnot grpmax-eligible | 0.00312% | 32,019 |
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.Thr675=
- Coding
- c.2025G>A
- MANE Select
- NM_002160
- Type
- single nucleotide variant
- Location
- chr9:115084315 (GRCh38)
- Gene constraint
- LOEUF 0.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.48 · 21 PDB
- Residue 675
- the fibronectin type-iii 1 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-thr675 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown