Is RTEL1 p.Ser300= (c.900C>T) pathogenic?

RTEL1 p.Ser300= (c.900C>T) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00865%, nfe); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Ser300= (c.900C>T)?

RTEL1 p.Ser300= (c.900C>T) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita (ClinVar).

How common is RTEL1 p.Ser300= (c.900C>T) in the general population?

RTEL1 p.Ser300= (c.900C>T) is very rare (popmax 0.00865%, nfe) (gnomAD).

RTEL1 p.Ser300=

c.900C>T · rs146100165 · VCV766054

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00865%, nfe)

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	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP -7.6	GERP -2.8
Overall
CADD	1.737	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00865% European (non-Finnish) · 102/1,179,542 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00682% 110/1,612,458 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00865%	11,564
Admixed American	0.00334%	29,939
Remaining individualsnot grpmax-eligible	0.00321%	31,193
Finnishnot grpmax-eligible	0.00314%	31,874
African / African-American	0.00134%	74,720
South Asian	0.0011%	90,938

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.Ser300=
Coding: c.900C>T
MANE Select: NM_001283009
dbSNP: rs146100165
Type: single nucleotide variant
Location: chr20:63674074 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 300: 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 dyskeratosis congenita

Similar variants

RTEL1 p.Ser300Arg Uncertain significance ★★ ⚠ same residue
RTEL1 p.Ser300Cys Uncertain significance ★ ⚠ same residue
RTEL1 p.Ser300Gly 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

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-ser300 (accessed [today's date]).

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