Is RTEL1 p.Thr997= (c.2991T>C) pathogenic?

RTEL1 p.Thr997= (c.2991T>C) is classified Uncertain significance in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-30). Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Thr997= (c.2991T>C)?

RTEL1 p.Thr997= (c.2991T>C) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Thr997= (c.2991T>C) in the general population?

RTEL1 p.Thr997= (c.2991T>C) is absent from gnomAD v4.1 (gnomAD).

RTEL1 p.Thr997=

c.2991T>C · rs2145449639 · VCV1418109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -2.5
Overall
CADD	0.188	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RTEL1
Protein: p.Thr997=
Coding: c.2991T>C
MANE Select: NM_001283009
dbSNP: rs2145449639
Type: single nucleotide variant
Location: chr20:63693282 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 997: 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.Thr997Ala Uncertain significance ★★ ⚠ same residue
RTEL1 p.Thr997Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
RTEL1 p.Thr997fs Pathogenic ★ same residue
RTEL1 p.Thr997Ile Uncertain significance ★ ⚠ same residue
RTEL1 p.Thr997Asn 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

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-thr997 (accessed [today's date]).

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