Is RTEL1 p.Ile248= (c.744C>A) pathogenic?

RTEL1 p.Ile248= (c.744C>A) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). Very rare (popmax 6.3e-05%); Associated with Inborn genetic diseases.

What condition is associated with RTEL1 p.Ile248= (c.744C>A)?

RTEL1 p.Ile248= (c.744C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RTEL1 p.Ile248= (c.744C>A) in the general population?

RTEL1 p.Ile248= (c.744C>A) is very rare (popmax 6.3e-05%) (gnomAD).

RTEL1 p.Ile248=

c.744C>A · VCV4629655

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.3e-05%)

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 0.72	GERP -0.051, phastCons 1
Overall
CADD	9.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.3e-05%

Overall 6.3e-05% 1/1,586,350 alleles · very rare exomes 1/1,433,992 · genomes 0/152,358 · 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.Ile248=
Coding: c.744C>A
MANE Select: NM_001283009
Type: single nucleotide variant
Location: chr20:63672600 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 248: 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

TNFRSF6B p.Ala248Val 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
RTEL1 p.Ala1240Pro 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-ile248 (accessed [today's date]).

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