TENM3 p.Pro399=
c.1197T>C · rs192736990 · VCV789177
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, 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 -0.079 | GERP -2.4, phastCons 0.85 |
| Overall | ||
| CADD | 7.188 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
Middle Eastern · 62/6,062 alleles
Filtering AF
0.981%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.975%
Overall
0.831%
13,395/1,612,876 alleles · low-frequency
exomes 12,549/1,460,572 · genomes 846/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.02% | 98 |
| European (non-Finnish) | 0.996% | 100 |
| Remaining individualsnot grpmax-eligible | 0.725% | 138 |
| South Asian | 0.677% | 148 |
| Finnishnot grpmax-eligible | 0.363% | 276 |
| Ashkenazi Jewishnot grpmax-eligible | 0.203% | 493 |
| Admixed American | 0.192% | 521 |
| African / African-American | 0.151% | 664 |
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.Pro399=
- Coding
- c.1197T>C
- MANE Select
- NM_001080477
- dbSNP
- rs192736990
- Type
- single nucleotide variant
- Location
- chr4:182673090 (GRCh38)
- Gene constraint
- LOEUF 0.305 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.76
Similar variants
- 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
- TENM3 p.Arg1494Gln 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-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown