Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 14 submitters
gnomAD v4.1
Common
common (popmax 94.3%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
3
dyskeratosis congenita, autosomal recessive 5
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 -5.5 | GERP -2.8 |
| Overall | ||
| CADD | 0.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
94.3%
African / African-American · 69,348/73,504 alleles
Filtering AF
93.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.5%
Overall
76.1%
1,181,912/1,553,268 alleles · common
exomes 1,059,519/1,401,142 · genomes 122,393/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 94.3% | 1 |
| Amishnot grpmax-eligible | 81.4% | 1 |
| Finnishnot grpmax-eligible | 80.3% | 1 |
| Middle Eastern | 78.1% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 77.1% | 1 |
| European (non-Finnish) | 76.6% | 1 |
| Remaining individualsnot grpmax-eligible | 75.1% | 1 |
| Admixed American | 74.9% | 1 |
| South Asian | 73.3% | 1 |
| East Asian | 30.5% | 3 |
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
- RTEL1
- Protein
- p.Pro848=
- Coding
- c.2544T>C
- MANE Select
- NM_001283009
- dbSNP
- rs3208007
- Type
- single nucleotide variant
- Location
- chr20:63690935 (GRCh38)
- Gene constraint
- LOEUF 0.661 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.64 · 3 PDB
- Residue 848
- the 'disordered' region
Similar variants
- RTEL1 c.1037+1G>T Likely pathogenic ★★ same condition
- RTEL1 c.1192-2A>G Likely pathogenic ★★ same condition
- RTEL1 c.1596-1G>A Likely pathogenic ★★ same condition
- RTEL1 c.2142-1G>C Likely pathogenic ★★ same condition
- RTEL1 c.2265+1G>T Likely pathogenic ★★ same condition
- RTEL1 c.2413+1G>A Likely pathogenic ★★ same condition
- RTEL1 c.2413+1G>C Pathogenic/Likely pathogenic ★★ same condition
- RTEL1 c.2557-2A>G Likely pathogenic ★★ 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/rtel1-p-pro848 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown