Is RTEL1 p.Pro985= (c.2955C>G) pathogenic?

RTEL1 p.Pro985= (c.2955C>G) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-18). Very rare (popmax 6.2e-05%); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Pro985= (c.2955C>G)?

RTEL1 p.Pro985= (c.2955C>G) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Pro985= (c.2955C>G) in the general population?

RTEL1 p.Pro985= (c.2955C>G) is very rare (popmax 6.2e-05%) (gnomAD).

RTEL1 p.Pro985=

c.2955C>G · rs2090808224 · VCV1544258

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -2.9
Overall
CADD	0.179	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,611,968 alleles · very rare exomes 1/1,459,818 · genomes 0/152,150 · 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.Pro985=
Coding: c.2955C>G
MANE Select: NM_001283009
dbSNP: rs2090808224
Type: single nucleotide variant
Location: chr20:63693246 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 985: 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.Pro985Arg Uncertain significance ★ ⚠ same residue
RTEL1 p.Pro985His Uncertain significance ★ ⚠ same residue
RTEL1 p.Pro985Thr Uncertain significance ★ ⚠ same residue
RTEL1 p.Pro985Leu Uncertain significance ★ ⚠ same residue
RTEL1 p.Pro985Ala 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-pro985 (accessed [today's date]).

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