Is RTEL1 p.Pro1297= (c.3891A>G) pathogenic?

RTEL1 p.Pro1297= (c.3891A>G) is classified Benign/Likely benign in RTEL1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 9.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

RTEL1 p.Pro1297=

Q: What condition is associated with RTEL1 p.Pro1297= (c.3891A>G)?

RTEL1 p.Pro1297= (c.3891A>G) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

Q: How common is RTEL1 p.Pro1297= (c.3891A>G) in the general population?

RTEL1 p.Pro1297= (c.3891A>G) is common (popmax 9.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3891A>G · rs1056990 · VCV1170799

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 9.5%, nfe) — too common for a highly-penetrant pathogenic allele

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 -6.5	GERP -2.9
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.5% European (non-Finnish) · 111,170/1,170,604 alleles

Filtering AF 9.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.43%

Overall 8.07% 128,464/1,591,698 alleles · common exomes 119,510/1,439,416 · genomes 8,954/152,282 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	9.5%	11
Amishnot grpmax-eligible	8.77%	11
Remaining individualsnot grpmax-eligible	7.37%	14
Ashkenazi Jewishnot grpmax-eligible	7.02%	14
Finnishnot grpmax-eligible	6.63%	15
Middle Eastern	5.41%	18
Admixed American	3.64%	27
South Asian	3.53%	28
African / African-American	1.52%	66
East Asian	0.0249%	4,018

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.Pro1297=
Coding: c.3891A>G
MANE Select: NM_001283009
dbSNP: rs1056990
Type: single nucleotide variant
Location: chr20:63695846 (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.Pro1297Ser 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
RTEL1 c.2265+1G>T Likely pathogenic ★★ same condition
RTEL1 c.2413+1G>A Likely pathogenic ★★ same condition
RTEL1 c.2413+1G>C Pathogenic/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-pro1297 (accessed [today's date]).

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