Is RTEL1 p.Arg895= (c.2685G>A) pathogenic?

RTEL1 p.Arg895= (c.2685G>A) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Ultra-rare (popmax 0.0165%, mid); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Arg895= (c.2685G>A) in the general population?

RTEL1 p.Arg895= (c.2685G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RTEL1 p.Arg895=

Q: What condition is associated with RTEL1 p.Arg895= (c.2685G>A)?

RTEL1 p.Arg895= (c.2685G>A) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.2685G>A · VCV3748179

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.8, phastCons 1
Overall
CADD	0.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,612,452 alleles · ultra-rare exomes 3/1,460,226 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
African / African-American	0.004%	24,978

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.Arg895=
Coding: c.2685G>A
MANE Select: NM_001283009
Type: single nucleotide variant
Location: chr20:63692837 (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.Arg895Gly Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg895Lys Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg895Thr Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg895Trp 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-arg895 (accessed [today's date]).

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