TNC p.Ser1703=
c.5109T>C · rs139558312 · VCV2659454
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.241 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 2.9, phastCons 1 |
| Overall | ||
| CADD | 9.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
European (non-Finnish) · 196/1,179,964 alleles
Filtering AF
0.0147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.014%
Overall
0.0126%
204/1,613,942 alleles · ultra-rare
exomes 194/1,461,810 · genomes 10/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0166% | 6,020 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Finnishnot grpmax-eligible | 0.00312% | 32,015 |
| African / African-American | 0.00267% | 37,447 |
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.Ser1703=
- Coding
- c.5109T>C
- MANE Select
- NM_002160
- dbSNP
- rs139558312
- Type
- single nucleotide variant
- Location
- chr9:115046426 (GRCh38)
- Gene constraint
- LOEUF 0.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.48 · 21 PDB
- Residue 1703
- the fibronectin type-iii 12 domain
Similar variants
- TNC p.Ser1703Asn Uncertain significance ★ ⚠ same residue
- 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
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-ser1703 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown