Is RTEL1 p.Phe709= (c.2127C>T) pathogenic?

RTEL1 p.Phe709= (c.2127C>T) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). Ultra-rare (popmax 0.0165%, mid); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Phe709= (c.2127C>T) in the general population?

RTEL1 p.Phe709= (c.2127C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RTEL1 p.Phe709=

Q: What condition is associated with RTEL1 p.Phe709= (c.2127C>T)?

RTEL1 p.Phe709= (c.2127C>T) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.2127C>T · rs866837044 · VCV748469

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.034	GERP 0.22, phastCons 0.078
Overall
CADD	18.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,070 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000373% 6/1,609,370 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,070
African / African-American	0.00267%	37,457
South Asian	0.0022%	45,539
Finnishnot grpmax-eligible	0.00167%	59,900

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.Phe709=
Coding: c.2127C>T
MANE Select: NM_001283009
dbSNP: rs866837044
Type: single nucleotide variant
Location: chr20:63689851 (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 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
RTEL1 c.2557-2A>G 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-phe709 (accessed [today's date]).

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