Is RTEL1 p.Asp704= (c.2112C>T) pathogenic?

RTEL1 p.Asp704= (c.2112C>T) is classified Benign in RTEL1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 14.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Asp704= (c.2112C>T)?

RTEL1 p.Asp704= (c.2112C>T) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita (ClinVar).

RTEL1 p.Asp704=

Q: How common is RTEL1 p.Asp704= (c.2112C>T) in the general population?

RTEL1 p.Asp704= (c.2112C>T) is common (popmax 14.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2112C>T · rs61753459 · VCV403399

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 14.3%, mid) — too common for a highly-penetrant pathogenic allele

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 1.7	GERP -1.1, phastCons 1
Overall
CADD	16.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.3% Middle Eastern · 863/6,054 alleles

Filtering AF 13.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 8.18% 131,748/1,610,866 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	14.3%	7
South Asian	12.3%	8
Ashkenazi Jewishnot grpmax-eligible	12%	8
European (non-Finnish)	8.53%	12
Finnishnot grpmax-eligible	8.42%	12
Remaining individualsnot grpmax-eligible	8.29%	12
Admixed American	6.56%	15
Amishnot grpmax-eligible	1.64%	61
African / African-American	1.56%	64
East Asian	0.0446%	2,243

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.Asp704=
Coding: c.2112C>T
MANE Select: NM_001283009
dbSNP: rs61753459
Type: single nucleotide variant
Location: chr20:63689836 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB

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.Asp704Asn 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
RTEL1 c.2413+1G>A Likely pathogenic ★★ same condition
RTEL1 c.2413+1G>C Pathogenic/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-asp704 (accessed [today's date]).

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