TSEN2 p.Pro218=
c.654C>G · rs142436743 · VCV2860999
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00547%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.65, phastCons 0.001 |
| Overall | ||
| CADD | 3.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00547%
European (non-Finnish) · 64/1,169,714 alleles
Filtering AF
0.00438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00399%
Overall
0.00414%
66/1,595,502 alleles · very rare
exomes 64/1,443,382 · genomes 2/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00547% | 18,277 |
| Remaining individualsnot grpmax-eligible | 0.00324% | 30,819 |
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.Pro218=
- Coding
- c.654C>G
- MANE Select
- NM_025265
- dbSNP
- rs142436743
- Type
- single nucleotide variant
- Location
- chr3:12503607 (GRCh38)
- Gene constraint
- LOEUF 1.212 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.63 · 5 PDB
Similar variants
- TSEN2 p.Pro218Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown