Is RTEL1 p.Phe560del (c.1675TTC[1]) pathogenic?

RTEL1 p.Phe560del (c.1675TTC[1]) is classified Uncertain significance in RTEL1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-02-19). Very rare (popmax 0.0011%, sas); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Phe560del (c.1675TTC[1])?

RTEL1 p.Phe560del (c.1675TTC[1]) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Phe560del (c.1675TTC[1]) in the general population?

RTEL1 p.Phe560del (c.1675TTC[1]) is very rare (popmax 0.0011%, sas) (gnomAD).

RTEL1 p.Phe560del

c.1675TTC[1] · rs779176651 · VCV557784

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP -0.79, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000959% 14/1,460,318 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.00102%	98,327

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe560del
Coding: c.1675TTC[1]
MANE Select: NM_001283009
dbSNP: rs779176651
Type: Microsatellite
Location: chr20:63688337 (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

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.Phe560Leu Uncertain significance ★ ⚠ same residue
RTEL1 p.Phe1184fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Ala95_Ala96dup Uncertain significance ★★ same condition
RTEL1 p.Lys877del Uncertain significance ★★ same condition
RTEL1 p.Glu771del Benign/Likely benign ★★ same condition
RTEL1 p.Ala1259fs Pathogenic ★ same condition
RTEL1 p.Asp105fs Likely pathogenic ★ same condition
RTEL1 p.Glu154_Ser155insTer 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-phe560del (accessed [today's date]).

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