Is RTEL1 p.Arg989Trp (c.2965C>T) pathogenic?

RTEL1 p.Arg989Trp (c.2965C>T) is classified Conflicting classifications of pathogenicity in RTEL1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0792); Ultra-rare (popmax 0.0627%, afr); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

What condition is associated with RTEL1 p.Arg989Trp (c.2965C>T)?

RTEL1 p.Arg989Trp (c.2965C>T) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5, dyskeratosis congenita (ClinVar).

How common is RTEL1 p.Arg989Trp (c.2965C>T) in the general population?

RTEL1 p.Arg989Trp (c.2965C>T) is ultra-rare (popmax 0.0627%, afr) (gnomAD).

What do computational predictors say about RTEL1 p.Arg989Trp (c.2965C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

RTEL1 p.Arg989Trp

c.2965C>T · rs139221232 · VCV967770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.7	GERP -2.6
Regional constraint	o/e 1.45	unconstrained · MANE · 5,558 bp · p 3.7e-34 · regional, not allelic
Overall
CADD	2.229	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0627% African / African-American · 47/74,936 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.0266% 429/1,611,880 alleles · ultra-rare exomes 382/1,459,736 · genomes 47/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0627%	1,594
South Asian	0.0428%	2,336
East Asian	0.0334%	2,992
Middle Eastern	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.032%	3,122
European (non-Finnish)	0.0239%	4,182
Admixed American	0.0217%	4,612
Finnishnot grpmax-eligible	0.016%	6,262
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,562

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.Arg989Trp
Coding: c.2965C>T
MANE Select: NM_001283009
dbSNP: rs139221232
Type: single nucleotide variant
Location: chr20:63693256 (GRCh38)

Full RTEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal recessive 5 dyskeratosis congenita

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-arg989trp (accessed [today's date]).

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