Is RTEL1 p.Ser925= (c.2775C>T) pathogenic?

RTEL1 p.Ser925= (c.2775C>T) is classified Benign/Likely benign in RTEL1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Low-frequency (popmax 4.63%, amr); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

What condition is associated with RTEL1 p.Ser925= (c.2775C>T)?

RTEL1 p.Ser925= (c.2775C>T) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5, dyskeratosis congenita (ClinVar).

How common is RTEL1 p.Ser925= (c.2775C>T) in the general population?

RTEL1 p.Ser925= (c.2775C>T) is low-frequency (popmax 4.63%, amr) (gnomAD).

RTEL1 p.Ser925=

c.2775C>T · rs12480346 · VCV436569

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.63%, amr)

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 carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.1
Overall
CADD	0.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.63% Admixed American · 2,776/60,004 alleles

Filtering AF 4.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.42%

Overall 0.26% 4,192/1,612,652 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.63%	22
East Asian	0.504%	199
Ashkenazi Jewishnot grpmax-eligible	0.358%	279
Middle Eastern	0.281%	356
Remaining individualsnot grpmax-eligible	0.279%	359
South Asian	0.233%	430
African / African-American	0.0813%	1,230
European (non-Finnish)	0.0521%	1,918
Finnishnot grpmax-eligible	0.00797%	12,542

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.Ser925=
Coding: c.2775C>T
MANE Select: NM_001283009
dbSNP: rs12480346
Type: single nucleotide variant
Location: chr20:63692927 (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 dyskeratosis congenita

Similar variants

RTEL1 p.Ser925Tyr Uncertain significance ★★ ⚠ same residue
RTEL1 p.Ser925Cys Uncertain significance ★ ⚠ same residue
RTEL1 p.Ser925Phe 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-ser925 (accessed [today's date]).

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