Is RTEL1 p.Ser1183= (c.3549C>T) pathogenic?

RTEL1 p.Ser1183= (c.3549C>T) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). Ultra-rare (popmax 0.0158%, eas); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Ser1183= (c.3549C>T)?

RTEL1 p.Ser1183= (c.3549C>T) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Ser1183= (c.3549C>T) in the general population?

RTEL1 p.Ser1183= (c.3549C>T) is ultra-rare (popmax 0.0158%, eas) (gnomAD).

RTEL1 p.Ser1183=

c.3549C>T · rs775274392 · VCV1126625

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, eas)

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.28	GERP -2.7, phastCons 0.018
Overall
CADD	15.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0158% East Asian · 7/44,278 alleles

Filtering AF 0.00735% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0052%

Overall 0.000574% 8/1,393,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0158%	6,325
South Asian	0.00124%	80,586

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.Ser1183=
Coding: c.3549C>T
MANE Select: NM_001283009
dbSNP: rs775274392
Type: single nucleotide variant
Location: chr20:63695377 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 1183: the 'disordered' region

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.Ser1183Phe Uncertain significance ★★ ⚠ same residue
RTEL1 p.Ser1183Thr 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-ser1183 (accessed [today's date]).

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