TELO2 p.Ala121=
c.363G>A · rs746430058 · VCV3040594
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00479%, eas)
Conditions
1
TELO2-related disorder
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 -7.6 | GERP -4.6 |
| Overall | ||
| CADD | 0.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00479%
East Asian · 2/41,714 alleles
Filtering AF
0.0035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00317%
Overall
0.00365%
57/1,560,494 alleles · very rare
exomes 53/1,408,270 · genomes 4/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00479% | 20,857 |
| European (non-Finnish) | 0.00451% | 22,168 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,318 |
| African / African-American | 0.00136% | 73,520 |
| South Asian | 0.00116% | 85,894 |
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
- TELO2
- Protein
- p.Ala121=
- Coding
- c.363G>A
- MANE Select
- NM_016111
- dbSNP
- rs746430058
- Type
- single nucleotide variant
- Location
- chr16:1495373 (GRCh38)
- Gene constraint
- LOEUF 1.03 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.74 · 4 PDB
- Residue 121
- an α-helix
Disease context
TELO2-related disorder
Similar variants
- TELO2 p.Ala121Val Uncertain significance ★ ⚠ same residue
- TELO2 c.2291+1G>C Likely pathogenic ★★ same condition
- TELO2 p.Leu771Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
- TELO2 p.His224= Likely benign same condition
- TELO2 c.2034+2T>C Likely pathogenic ★★ same type
- TELO2 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same type
- TELO2 p.Arg609His Pathogenic/Likely pathogenic ★★ same type
- TELO2 p.Cys367Phe Pathogenic/Likely pathogenic ★★ 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/telo2-p-ala121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown