Is RTEL1 p.Cys51Ser (c.152G>C) pathogenic?

RTEL1 p.Cys51Ser (c.152G>C) is classified Uncertain significance in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-08). AlphaMissense: ambiguous (0.4865); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RTEL1 p.Cys51Ser (c.152G>C)?

RTEL1 p.Cys51Ser (c.152G>C) is associated with Inborn genetic diseases (ClinVar).

How common is RTEL1 p.Cys51Ser (c.152G>C) in the general population?

RTEL1 p.Cys51Ser (c.152G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RTEL1 p.Cys51Ser (c.152G>C)?

AlphaMissense predicts ambiguous (score 0.4865) — an in-silico prediction, not a clinical call.

RTEL1 p.Cys51Ser

c.152G>C · VCV3436046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4865 · ACMG-weighted

gnomAD v4.1

Rare

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

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4865	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -8.63	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 31 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.85e-05% 1/1,460,884 alleles · very rare

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.Cys51Ser
Coding: c.152G>C
MANE Select: NM_001283009
Type: single nucleotide variant
Location: chr20:63661347 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 51: 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.Cys51= Likely benign ★★ 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-cys51ser (accessed [today's date]).

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