Is RTEL1 p.Arg1127Ser (c.3379C>A) pathogenic?

RTEL1 p.Arg1127Ser (c.3379C>A) is classified Uncertain significance in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-14). AlphaMissense: likely benign (0.1905); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Arg1127Ser (c.3379C>A)?

RTEL1 p.Arg1127Ser (c.3379C>A) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Arg1127Ser (c.3379C>A) in the general population?

RTEL1 p.Arg1127Ser (c.3379C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTEL1 p.Arg1127Ser (c.3379C>A)?

AlphaMissense predicts likely benign (score 0.1905) — an in-silico prediction, not a clinical call.

RTEL1 p.Arg1127Ser

c.3379C>A · rs745614952 · VCV839025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
AlphaMissense	0.1905	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP -2.9, phastCons 0.079
Regional constraint	o/e 1.45	unconstrained · MANE · 5,558 bp · p 3.7e-34 · regional, not allelic
Overall
CADD	16.96	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.Arg1127Ser
Coding: c.3379C>A
MANE Select: NM_001283009
dbSNP: rs745614952
Type: single nucleotide variant
Location: chr20:63695101 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 1127: an α-helix

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.Arg1127Cys Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg1127His Uncertain significance ★★ ⚠ same residue
RTEL1 p.Arg1127= Conflicting classifications of pathogenicity ★ same residue
RTEL1 p.Arg1127Gly 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

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-arg1127ser (accessed [today's date]).

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