Is RTEL1 p.Thr786= (c.2358C>T) pathogenic?

RTEL1 p.Thr786= (c.2358C>T) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-23). Ultra-rare (popmax 0.0441%, afr); Associated with Inborn genetic diseases.

How common is RTEL1 p.Thr786= (c.2358C>T) in the general population?

RTEL1 p.Thr786= (c.2358C>T) is ultra-rare (popmax 0.0441%, afr) (gnomAD).

RTEL1 p.Thr786=

Q: What condition is associated with RTEL1 p.Thr786= (c.2358C>T)?

RTEL1 p.Thr786= (c.2358C>T) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

c.2358C>T · rs202106904 · VCV540954

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.061	GERP -2.5, phastCons 0.051
Overall
CADD	8.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0441% African / African-American · 33/74,880 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00211% 34/1,611,192 alleles · ultra-rare exomes 19/1,459,236 · genomes 15/151,956 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0441%	2,269
Remaining individualsnot grpmax-eligible	0.0016%	62,406

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.Thr786=
Coding: c.2358C>T
MANE Select: NM_001283009
dbSNP: rs202106904
Type: single nucleotide variant
Location: chr20:63690386 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 786: the 'disordered' region

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

Also linked: dyskeratosis congenita, autosomal recessive 5 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

Similar variants

RTEL1 p.Thr786Ala Uncertain significance ★ ⚠ same residue
RTEL1 p.Thr786Ile Uncertain significance ★ ⚠ same residue
RTEL1 p.Thr786Ser Uncertain significance ★ ⚠ same residue
RTEL1 c.1037+1G>T Likely pathogenic ★★ same condition
RTEL1 c.1192-2A>G Likely pathogenic ★★ same condition
RTEL1 c.1596-1G>A Likely pathogenic ★★ same condition
RTEL1 c.2142-1G>C Likely pathogenic ★★ same condition
RTEL1 c.2265+1G>T 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-thr786 (accessed [today's date]).

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