Is RTEL1 p.Ala1001= (c.3003G>A) pathogenic?

RTEL1 p.Ala1001= (c.3003G>A) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-08). Very rare (popmax 0.00695%, nfe); Associated with Inborn genetic diseases.

How common is RTEL1 p.Ala1001= (c.3003G>A) in the general population?

RTEL1 p.Ala1001= (c.3003G>A) is very rare (popmax 0.00695%, nfe) (gnomAD).

RTEL1 p.Ala1001=

Q: What condition is associated with RTEL1 p.Ala1001= (c.3003G>A)?

RTEL1 p.Ala1001= (c.3003G>A) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

c.3003G>A · rs368070468 · VCV436576

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.089	GERP -2.5
Overall
CADD	4.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% European (non-Finnish) · 82/1,179,316 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00558% 90/1,611,560 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,382
Admixed American	0.00667%	14,988
Remaining individualsnot grpmax-eligible	0.0016%	62,410
Finnishnot grpmax-eligible	0.0016%	62,604
African / African-American	0.00134%	74,826
South Asian	0.0011%	91,064

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.Ala1001=
Coding: c.3003G>A
dbSNP: rs368070468
Type: single nucleotide variant
Location: chr20:63694382 (GRCh38)

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

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-ala1001 (accessed [today's date]).

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