TELO2 p.Asp448=
c.1344C>T · rs370665424 · VCV2645901
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.80 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -4.5 |
| Overall | ||
| CADD | 7.717 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00236%
38/1,610,038 alleles · ultra-rare
exomes 27/1,457,846 · genomes 11/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| Admixed American | 0.0117% | 8,525 |
| East Asian | 0.00446% | 22,404 |
| African / African-American | 0.00401% | 24,953 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,159 |
| South Asian | 0.0022% | 45,383 |
| European (non-Finnish) | 0.00161% | 62,026 |
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.Asp448=
- Coding
- c.1344C>T
- MANE Select
- NM_016111
- dbSNP
- rs370665424
- Type
- single nucleotide variant
- Location
- chr16:1501482 (GRCh38)
- Gene constraint
- LOEUF 1.03 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.74 · 4 PDB
- Residue 448
- the 'disordered' region
Similar variants
- TELO2 c.2034+2T>C Likely pathogenic ★★ same type
- TELO2 c.2291+1G>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
- TELO2 c.830+5G>T Uncertain significance ★★ same type
- TELO2 p.Ala198Val Uncertain significance ★★ ⚠ same type
- TELO2 p.Ala323Pro 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/telo2-p-asp448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown