TNC p.Ala2009=
c.6027G>C · VCV4904246
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.222 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -5.8 |
| Overall | ||
| CADD | 0.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
African / African-American · 38/75,034 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0334%
Overall
0.00285%
46/1,613,488 alleles · ultra-rare
exomes 23/1,461,218 · genomes 23/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0506% | 1,975 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,490 |
| Admixed American | 0.00333% | 30,002 |
| South Asian | 0.0011% | 91,020 |
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.Ala2009=
- Coding
- c.6027G>C
- MANE Select
- NM_002160
- Type
- single nucleotide variant
- Location
- chr9:115030299 (GRCh38)
- Gene constraint
- LOEUF 0.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.48 · 21 PDB
- Residue 2009
- a β-strand; the fibrinogen c-terminal 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-ala2009 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown