Is RTEL1 p.Pro757fs (c.2270del) pathogenic?

RTEL1 p.Pro757fs (c.2270del) is classified Pathogenic in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-24). No gnomAD frequency available for this variant; Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Pro757fs (c.2270del) in the general population?

RTEL1 p.Pro757fs (c.2270del) is no gnomAD frequency available for this variant (gnomAD).

RTEL1 p.Pro757fs

Q: What condition is associated with RTEL1 p.Pro757fs (c.2270del)?

RTEL1 p.Pro757fs (c.2270del) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.2270del · rs2145431569 · VCV1443666

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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

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 8.3	GERP 0.28, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RTEL1
Protein: p.Pro757fs
Coding: c.2270del
MANE Select: NM_001283009
dbSNP: rs2145431569
Type: Deletion
Location: chr20:63690297 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 757: the 'disordered' region

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

Disease context

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal recessive 5

Similar variants

RTEL1 p.Pro757Ser Uncertain significance ★★ ⚠ same residue
RTEL1 p.Pro757Thr Uncertain significance ★★ ⚠ same residue
RTEL1 c.1236_1266+47del Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg733fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg879fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg986fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Asn637fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Gln1187fs Pathogenic/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-pro757fs (accessed [today's date]).

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