Is RTEL1 p.Thr56= (c.168G>A) pathogenic?

RTEL1 p.Thr56= (c.168G>A) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). Ultra-rare (popmax 0.0725%, sas); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Thr56= (c.168G>A)?

RTEL1 p.Thr56= (c.168G>A) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Thr56= (c.168G>A) in the general population?

RTEL1 p.Thr56= (c.168G>A) is ultra-rare (popmax 0.0725%, sas) (gnomAD).

RTEL1 p.Thr56=

c.168G>A · rs776722400 · VCV1091380

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0725%, sas)

Conditions

dyskeratosis congenita, autosomal recessive 5

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 -6.2	GERP -3.2
Overall
CADD	0.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0725% South Asian · 66/91,058 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00539% 87/1,613,556 alleles · ultra-rare exomes 80/1,461,210 · genomes 7/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0725%	1,380
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,456
Finnishnot grpmax-eligible	0.00157%	63,800
European (non-Finnish)	0.00144%	69,414
African / African-American	0.00133%	75,052

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.Thr56=
Coding: c.168G>A
MANE Select: NM_001283009
dbSNP: rs776722400
Type: single nucleotide variant
Location: chr20:63661363 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 56: the helicase atp-binding domain

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

Disease context

dyskeratosis congenita, autosomal recessive 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

Similar variants

RTEL1 p.Thr56Ala Uncertain significance ★ ⚠ same residue
RTEL1 p.Thr56Met Uncertain significance ⚠ same residue
RTEL1 p.Thr56Lys 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-thr56 (accessed [today's date]).

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