Is RTEL1 p.Pro884= (c.2652G>A) pathogenic?

RTEL1 p.Pro884= (c.2652G>A) is classified Uncertain significance in RTEL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-17). Very rare (popmax 0.004%, afr); Associated with dyskeratosis congenita.

How common is RTEL1 p.Pro884= (c.2652G>A) in the general population?

RTEL1 p.Pro884= (c.2652G>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RTEL1 p.Pro884=

Q: What condition is associated with RTEL1 p.Pro884= (c.2652G>A)?

RTEL1 p.Pro884= (c.2652G>A) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

c.2652G>A · rs201784607 · VCV1692621

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.31	donor loss · deltas
Pangolin	Δ0.54	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.1	GERP -2.3, phastCons 1
Overall
CADD	17.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,000 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00267% 43/1,608,974 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,000
European (non-Finnish)	0.00314%	31,868
Finnishnot grpmax-eligible	0.00167%	59,982
Remaining individualsnot grpmax-eligible	0.0016%	62,410
South Asian	0.0011%	91,052

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.Pro884=
Coding: c.2652G>A
MANE Select: NM_001283009
dbSNP: rs201784607
Type: single nucleotide variant
Location: chr20:63691837 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal recessive 5 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

RTEL1 p.Pro884Arg Uncertain significance ★★ ⚠ same residue
RTEL1 p.Pro884Leu 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

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-pro884 (accessed [today's date]).

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