Is RTEL1 p.Arg697Ter (c.2089C>T) pathogenic?

RTEL1 p.Arg697Ter (c.2089C>T) is classified Pathogenic/Likely pathogenic in RTEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-08). Very rare (popmax 0.000763%, nfe); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Arg697Ter (c.2089C>T) in the general population?

RTEL1 p.Arg697Ter (c.2089C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

RTEL1 p.Arg697Ter

Q: What condition is associated with RTEL1 p.Arg697Ter (c.2089C>T)?

RTEL1 p.Arg697Ter (c.2089C>T) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.2089C>T · rs768188490 · VCV959673

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 35
Splicing
SpliceAI	Δ0.55	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.3	GERP -1.3, phastCons 0.99
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,772 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,611,870 alleles · very rare exomes 8/1,459,712 · genomes 1/152,158 · 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.Arg697Ter
Coding: c.2089C>T
MANE Select: NM_001283009
dbSNP: rs768188490
Type: single nucleotide variant
Location: chr20:63689813 (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

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.Arg697Leu Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg697Gln Uncertain significance ★ ⚠ same residue
RTEL1 p.Arg697= Likely benign ★ same residue
RTEL1 p.Arg697Gly Uncertain significance ★ ⚠ same residue
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

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-arg697ter (accessed [today's date]).

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