Is RTEL1 p.Pro297= (c.891G>A) pathogenic?

RTEL1 p.Pro297= (c.891G>A) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-30). Ultra-rare (popmax 0.0361%, afr); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Pro297= (c.891G>A) in the general population?

RTEL1 p.Pro297= (c.891G>A) is ultra-rare (popmax 0.0361%, afr) (gnomAD).

RTEL1 p.Pro297=

Q: What condition is associated with RTEL1 p.Pro297= (c.891G>A)?

RTEL1 p.Pro297= (c.891G>A) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.891G>A · rs771117146 · VCV1136064

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0361%, afr)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.074	GERP -1.2
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0361% African / African-American · 27/74,738 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00347% 56/1,613,130 alleles · ultra-rare exomes 40/1,460,978 · genomes 16/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0361%	2,768
Middle Eastern	0.0333%	3,006
South Asian	0.00659%	15,171
Remaining individualsnot grpmax-eligible	0.00481%	20,805
European (non-Finnish)	0.00153%	65,545

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.Pro297=
Coding: c.891G>A
MANE Select: NM_001283009
dbSNP: rs771117146
Type: single nucleotide variant
Location: chr20:63674065 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 297: 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.Pro297Ala Uncertain significance ★★ ⚠ same residue
RTEL1 p.Pro297Ser Uncertain significance ★★ ⚠ same residue
RTEL1 p.Pro297Leu Conflicting classifications of pathogenicity ★ ⚠ 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
RTEL1 c.2265+1G>T 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-pro297 (accessed [today's date]).

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