Is RTEL1 p.Arg762fs (c.2284dup) pathogenic?

RTEL1 p.Arg762fs (c.2284dup) is classified Likely pathogenic in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Very rare (popmax 8.51e-05%, nfe); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Arg762fs (c.2284dup)?

RTEL1 p.Arg762fs (c.2284dup) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Arg762fs (c.2284dup) in the general population?

RTEL1 p.Arg762fs (c.2284dup) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

RTEL1 p.Arg762fs

c.2284dup · VCV3587608

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -2.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,174,608 alleles

Overall 6.23e-05% 1/1,605,270 alleles · very rare exomes 1/1,453,012 · genomes 0/152,258 · joint denominator

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.Arg762fs
Coding: c.2284dup
MANE Select: NM_001283009
Type: Duplication
Location: chr20:63690306 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 762: the 'disordered' region

Full RTEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyskeratosis congenita, autosomal recessive 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

Similar variants

RTEL1 p.Arg762Gln Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg762Trp Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg762= Likely benign ★★ same residue
RTEL1 p.Pro980fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 c.2025+8dup Likely benign ★★ same condition
RTEL1 c.919+952_1192-509dup Likely pathogenic ★ same condition
RTEL1 p.Ala417fs Pathogenic ★ same condition
RTEL1 p.Ala687fs 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-arg762fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown