Is RTEL1 p.Val1193fs (c.3578del) pathogenic?

RTEL1 p.Val1193fs (c.3578del) is classified Likely pathogenic in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). Absent from gnomAD; Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Val1193fs (c.3578del)?

RTEL1 p.Val1193fs (c.3578del) is associated with dyskeratosis congenita, autosomal recessive 5 (ClinVar).

How common is RTEL1 p.Val1193fs (c.3578del) in the general population?

RTEL1 p.Val1193fs (c.3578del) is absent from gnomAD (gnomAD).

RTEL1 p.Val1193fs

c.3578del · rs2145479688 · VCV1679562

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dyskeratosis congenita, autosomal recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 34 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.24	GERP -1.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RTEL1
Protein: p.Val1193fs
Coding: c.3578del
MANE Select: NM_001283009
dbSNP: rs2145479688
Type: Deletion
Location: chr20:63695406 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 1193: 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

Similar variants

RTEL1 p.Val1193Gly Uncertain significance ★★ ⚠ same residue
RTEL1 p.Val1193= Likely benign ★ same residue
RTEL1 c.1236_1266+47del Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg733fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg879fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Arg986fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Asn637fs Pathogenic/Likely pathogenic ★★ same condition
RTEL1 p.Gln1187fs Pathogenic/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-val1193fs (accessed [today's date]).

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