TENM3 p.Ile1663Thr
c.4988T>C · rs773160754 · VCV2364989
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2024 | likely benign |
|---|---|---|
| REVEL | 0.629 | indeterminate |
| SaProt | LLR -8.44 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.85 | unconstrained · MANE · 174 kb · p 1.9e-10 · regional, not allelic |
| Overall | ||
| CADD | 23.1 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| African / African-American | 0.0147% | 6,823 |
| Admixed American | 0.01% | 10,001 |
| South Asian | 0.00989% | 10,114 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
| European (non-Finnish) | 0.00763% | 13,109 |
| Finnishnot grpmax-eligible | 0.00469% | 21,339 |
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.Ile1663Thr
- Coding
- c.4988T>C
- MANE Select
- NM_001080477
- dbSNP
- rs773160754
- Type
- single nucleotide variant
- Location
- chr4:182773567 (GRCh38)
- Gene constraint
- LOEUF 0.305 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.76
- Residue 1663
- a UniProt-annotated variant site (in mcops15)
Similar variants
- TENM3 p.Ala1056Gly Uncertain significance ★★ ⚠ same condition
- TENM3 p.Ala1397Thr Uncertain significance ★★ ⚠ same condition
- TENM3 p.Ala1397Val Uncertain significance ★★ ⚠ same condition
- TENM3 p.Ala2168Val Uncertain significance ★★ ⚠ same condition
- TENM3 p.Ala864Ser Uncertain significance ★★ ⚠ same condition
- TENM3 p.Arg1341Cys Uncertain significance ★★ ⚠ same condition
- TENM3 p.Arg1494Gln Uncertain significance ★★ same condition
- TENM3 p.Asn601Lys Uncertain significance ★★ ⚠ same condition
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-ile1663thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown