Is RTEL1 p.Asp744= (c.2232C>T) pathogenic?

RTEL1 p.Asp744= (c.2232C>T) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

How common is RTEL1 p.Asp744= (c.2232C>T) in the general population?

RTEL1 p.Asp744= (c.2232C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

RTEL1 p.Asp744=

Q: What condition is associated with RTEL1 p.Asp744= (c.2232C>T)?

RTEL1 p.Asp744= (c.2232C>T) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

c.2232C>T · rs146666432 · VCV728463

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Inborn genetic diseases

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 -6.9	GERP -3.2
Overall
CADD	0.405	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,920 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00633% 102/1,612,428 alleles · ultra-rare exomes 91/1,460,250 · genomes 11/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,811
European (non-Finnish)	0.00729%	13,719
East Asian	0.00446%	22,445
Remaining individualsnot grpmax-eligible	0.0032%	31,226
Finnishnot grpmax-eligible	0.00159%	62,700

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.Asp744=
Coding: c.2232C>T
MANE Select: NM_001283009
dbSNP: rs146666432
Type: single nucleotide variant
Location: chr20:63690177 (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

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 dyskeratosis congenita

Similar variants

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
RTEL1 c.2557-2A>G 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-asp744 (accessed [today's date]).

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