RTEL1 p.Ala1226Val
c.3677C>T · VCV3948293
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000763%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.083 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -1.4 |
| Regional constraint | o/e 1.45 | unconstrained · MANE · 5,558 bp · p 3.7e-34 · regional, not allelic |
| Overall | ||
| CADD | 0.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000763%
European (non-Finnish) · 9/1,179,358 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000617%
9/1,459,138 alleles · very rare
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.Ala1226Val
- Coding
- c.3677C>T
- MANE Select
- NM_001283009
- Type
- single nucleotide variant
- Location
- chr20:63695505 (GRCh38)
- Gene constraint
- LOEUF 0.661 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.64 · 3 PDB
Similar variants
- RTEL1 p.Ala1226Ser Uncertain significance ★★ same residue
- RTEL1 p.Ala1226= Likely benign ★ same residue
- RTEL1 p.Ala1012Ser Uncertain significance ★★ ⚠ same condition
- RTEL1 p.Ala1052Thr Uncertain significance ★★ ⚠ same condition
- RTEL1 p.Ala1074Val Uncertain significance ★★ ⚠ same condition
- RTEL1 p.Ala1085Val Uncertain significance ★★ ⚠ same condition
- RTEL1 p.Ala1101Thr Uncertain significance ★★ ⚠ same condition
- RTEL1 p.Ala112Val Uncertain significance ★★ ⚠ 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-ala1226val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown