TSEN2 p.Pro356=
c.1068C>T · rs372715638 · VCV681107
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0294%, afr)
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 2.1 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 12.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0294%
African / African-American · 22/74,918 alleles
Filtering AF
0.0199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.00167%
27/1,614,048 alleles · ultra-rare
exomes 11/1,461,894 · genomes 16/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0294% | 3,405 |
| Admixed American | 0.005% | 19,998 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
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
- TSEN2
- Protein
- p.Pro356=
- Coding
- c.1068C>T
- MANE Select
- NM_025265
- dbSNP
- rs372715638
- Type
- single nucleotide variant
- Location
- chr3:12519166 (GRCh38)
- Gene constraint
- LOEUF 1.212 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.63 · 5 PDB
- Residue 356
- a β-strand
Similar variants
- TSEN2 c.1099+1G>A Likely pathogenic ★★ same type
- TSEN2 p.Tyr19Ter Pathogenic/Likely pathogenic ★★ same type
- TSEN2 c.1249-3T>C Uncertain significance ★★ same type
- TSEN2 c.189+4A>G Uncertain significance ★★ same type
- TSEN2 p.Ala111Thr Uncertain significance ★★ ⚠ same type
- TSEN2 p.Ala227Val Uncertain significance ★★ ⚠ same type
- TSEN2 p.Ala54Val Uncertain significance ★★ ⚠ same type
- TSEN2 p.Arg396His 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/tsen2-p-pro356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown