Is RTEL1 p.Glu180= (c.540A>G) pathogenic?

RTEL1 p.Glu180= (c.540A>G) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with RTEL1 p.Glu180= (c.540A>G)?

RTEL1 p.Glu180= (c.540A>G) is associated with Inborn genetic diseases (ClinVar).

How common is RTEL1 p.Glu180= (c.540A>G) in the general population?

RTEL1 p.Glu180= (c.540A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

RTEL1 p.Glu180=

c.540A>G · VCV4863611

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

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 4.2	GERP -2.3, phastCons 1
Overall
CADD	8.975	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,613,962 alleles · very rare exomes 4/1,461,762 · genomes 0/152,200 · 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.Glu180=
Coding: c.540A>G
MANE Select: NM_001283009
Type: single nucleotide variant
Location: chr20:63666005 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 180: the helicase atp-binding domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RTEL1 p.Glu180Asp Uncertain significance ★★ ⚠ same residue
RTEL1 p.Glu180Gly Uncertain significance ★★ ⚠ same residue
RTEL1 p.Ala1012Ser Uncertain significance ★★ ⚠ same condition
RTEL1 p.Ala1052Thr Uncertain significance ★★ ⚠ same condition
RTEL1 p.Ala1074Val Uncertain significance ★★ ⚠ same condition
RTEL1 p.Ala1085Val Uncertain significance ★★ ⚠ same condition
RTEL1 p.Ala1101Thr Uncertain significance ★★ ⚠ same condition
RTEL1 p.Ala112Val Uncertain significance ★★ ⚠ 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-glu180 (accessed [today's date]).

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