Is RTEL1 p.His147fs (c.439del) pathogenic?

RTEL1 p.His147fs (c.439del) is classified Pathogenic in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-09). Very rare (popmax 8.47e-05%, nfe).

How common is RTEL1 p.His147fs (c.439del) in the general population?

RTEL1 p.His147fs (c.439del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RTEL1 p.His147fs

c.439del · rs2146153953 · VCV1676799

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 5 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.2e-05% 1/1,614,048 alleles · very rare exomes 1/1,461,806 · genomes 0/152,242 · joint denominator

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.His147fs
Coding: c.439del
MANE Select: NM_001283009
dbSNP: rs2146153953
Type: Deletion
Location: chr20:63662588 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 147: the helicase atp-binding domain

Full RTEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTEL1 p.His147Arg Uncertain significance ★ ⚠ same residue
RTEL1 c.1236_1266+47del Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Arg733fs Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Arg879fs Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Arg986fs Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Asn637fs Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Gln1187fs Pathogenic/Likely pathogenic ★★ same type
RTEL1 p.Glu981fs Pathogenic/Likely pathogenic ★★ same type

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-his147fs (accessed [today's date]).

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