Is RTEL1 p.Asp719= (c.2157C>T) pathogenic?

RTEL1 p.Asp719= (c.2157C>T) is classified Likely benign in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). Ultra-rare (popmax 0.0174%, afr); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Asp719= (c.2157C>T)?

RTEL1 p.Asp719= (c.2157C>T) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Asp719= (c.2157C>T) in the general population?

RTEL1 p.Asp719= (c.2157C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

RTEL1 p.Asp719=

c.2157C>T · rs752607917 · VCV1146456

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.8	GERP -3.2
Overall
CADD	0.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,914 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.0018% 29/1,611,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,763
Remaining individualsnot grpmax-eligible	0.00641%	15,611
South Asian	0.0022%	45,547
Admixed American	0.00167%	59,986
European (non-Finnish)	0.000763%	131,083

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.Asp719=
Coding: c.2157C>T
MANE Select: NM_001283009
dbSNP: rs752607917
Type: single nucleotide variant
Location: chr20:63690102 (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

Similar variants

RTEL1 p.Asp719Asn Uncertain significance ★★ ⚠ same residue
RTEL1 p.Asp719His Uncertain significance ★ ⚠ same residue
RTEL1 p.Asp719Glu 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-asp719 (accessed [today's date]).

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