Is RTEL1 p.Pro1031Ser (c.3091C>T) pathogenic?

RTEL1 p.Pro1031Ser (c.3091C>T) is classified Conflicting classifications of pathogenicity in RTEL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0668); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Pro1031Ser (c.3091C>T)?

RTEL1 p.Pro1031Ser (c.3091C>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.Pro1031Ser (c.3091C>T) in the general population?

RTEL1 p.Pro1031Ser (c.3091C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTEL1 p.Pro1031Ser (c.3091C>T)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

RTEL1 p.Pro1031Ser

c.3091C>T · rs912272913 · VCV1359103

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -2.5
Regional constraint	o/e 1.45	unconstrained · MANE · 5,558 bp · p 3.7e-34 · regional, not allelic
Overall
CADD	0.293	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RTEL1
Protein: p.Pro1031Ser
Coding: c.3091C>T
MANE Select: NM_001283009
dbSNP: rs912272913
Type: single nucleotide variant
Location: chr20:63694470 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 1031: 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.Pro1031Leu Uncertain significance ★★ ⚠ same residue
RTEL1 p.Pro1031= Likely benign ★★ same residue
RTEL1 p.Pro1031His 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-pro1031ser (accessed [today's date]).

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