Is RTEL1 p.Thr104= (c.312G>A) pathogenic?

RTEL1 p.Thr104= (c.312G>A) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-30). Ultra-rare (popmax 0.0117%, nfe); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Thr104= (c.312G>A)?

RTEL1 p.Thr104= (c.312G>A) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita (ClinVar).

How common is RTEL1 p.Thr104= (c.312G>A) in the general population?

RTEL1 p.Thr104= (c.312G>A) is ultra-rare (popmax 0.0117%, nfe) (gnomAD).

RTEL1 p.Thr104=

c.312G>A · rs1348086708 · VCV540925

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, nfe)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.6	GERP -2.8
Overall
CADD	2.855	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% European (non-Finnish) · 138/1,179,962 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00948%

Overall 0.00874% 141/1,614,024 alleles · ultra-rare exomes 141/1,461,814 · genomes 0/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0117%	8,550
Remaining individualsnot grpmax-eligible	0.0032%	31,254
South Asian	0.0011%	91,080

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.Thr104=
Coding: c.312G>A
MANE Select: NM_001283009
dbSNP: rs1348086708
Type: single nucleotide variant
Location: chr20:63661860 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 104: 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 dyskeratosis congenita

Similar variants

RTEL1 p.Thr104Lys Uncertain significance ★★ ⚠ same residue
RTEL1 p.Thr104Met Uncertain significance ★★ ⚠ same residue
RTEL1 p.Thr104Pro 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-thr104 (accessed [today's date]).

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