Is RTEL1 p.Val552fs (c.1653_1666delinsTGA) pathogenic?

RTEL1 p.Val552fs (c.16531666delinsTGA) is classified Likely pathogenic in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Val552fs (c.1653_1666delinsTGA)?

RTEL1 p.Val552fs (c.1653_1666delinsTGA) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

RTEL1 p.Val552fs

c.1653_1666delinsTGA · VCV3587603

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 20 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: RTEL1
Protein: p.Val552fs
Coding: c.1653_1666delinsTGA
MANE Select: NM_001283009
Type: Indel
Location: chr20:63688317 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB

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 c.1596-1_1596delinsAA Likely pathogenic ★ same condition
RTEL1 p.Gly936fs Likely pathogenic ★ same condition
RTEL1 p.Val956fs Pathogenic ★ same condition
RTEL1 c.1722+10_1722+11delinsTT Uncertain significance ★ same condition
RTEL1 c.3499+5_3499+6delinsTC Uncertain significance ★ same condition
RTEL1 p.Ala929Pro Uncertain significance ★ same condition
RTEL1 p.Asp704Asn Uncertain significance ★ same condition
RTEL1 p.Gln991Arg 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-val552fs (accessed [today's date]).

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