TENM3 p.Pro223=
c.669C>T · rs781215278 · VCV2181294
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0468%, eas)
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 7.7 | phastCons 1 |
| Overall | ||
| CADD | 16.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0468%
East Asian · 21/44,838 alleles
Filtering AF
0.0313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0263%
Overall
0.0049%
79/1,613,680 alleles · ultra-rare
exomes 74/1,461,710 · genomes 5/151,970 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0468% | 2,135 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| European (non-Finnish) | 0.00424% | 23,597 |
| Admixed American | 0.00333% | 29,997 |
| South Asian | 0.00329% | 30,355 |
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
- TENM3
- Protein
- p.Pro223=
- Coding
- c.669C>T
- MANE Select
- NM_001080477
- dbSNP
- rs781215278
- Type
- single nucleotide variant
- Location
- chr4:182601081 (GRCh38)
- Gene constraint
- LOEUF 0.305 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.76
- Residue 223
- the teneurin n-terminal domain; the 'disordered' region
Similar variants
- TENM3 p.Pro223Ser Uncertain significance ★ ⚠ same residue
- TENM3 p.Ala1056Gly Uncertain significance ★★ ⚠ same type
- TENM3 p.Ala1397Thr Uncertain significance ★★ ⚠ same type
- TENM3 p.Ala1397Val Uncertain significance ★★ ⚠ same type
- TENM3 p.Ala1469Val Uncertain significance ★★ ⚠ same type
- TENM3 p.Ala2168Val Uncertain significance ★★ ⚠ same type
- TENM3 p.Ala864Ser Uncertain significance ★★ ⚠ same type
- TENM3 p.Arg1341Cys 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/tenm3-p-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown