Is RTEL1 p.Arg986Ter (c.2956C>T) pathogenic?

RTEL1 p.Arg986Ter (c.2956C>T) is classified Pathogenic/Likely pathogenic in RTEL1 (ClinVar, Multiple submitters, 25 submitters; last evaluated 2026-01-29). Ultra-rare (popmax 0.0494%, mid); Associated with RTEL1-related disorder.

What condition is associated with RTEL1 p.Arg986Ter (c.2956C>T)?

RTEL1 p.Arg986Ter (c.2956C>T) is associated with RTEL1-related disorder, pulmonary fibrosis, Adams-Oliver syndrome 3 (ClinVar).

How common is RTEL1 p.Arg986Ter (c.2956C>T) in the general population?

RTEL1 p.Arg986Ter (c.2956C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

RTEL1 p.Arg986Ter

c.2956C>T · rs373740199 · VCV65417

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 25 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Conditions

RTEL1-related disorder

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.24	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP -3.1	GERP -2.9
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% Middle Eastern · 3/6,078 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.00521% 84/1,611,858 alleles · ultra-rare exomes 71/1,459,812 · genomes 13/152,046 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,026
Finnishnot grpmax-eligible	0.0128%	7,834
Remaining individualsnot grpmax-eligible	0.00961%	10,403
African / African-American	0.00802%	12,471
Admixed American	0.005%	19,982
European (non-Finnish)	0.00466%	21,445
East Asian	0.00445%	22,452
South Asian	0.0011%	91,094

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.Arg986Ter
Coding: c.2956C>T
MANE Select: NM_001283009
dbSNP: rs373740199
Type: single nucleotide variant
Location: chr20:63693247 (GRCh38)

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

Disease context

RTEL1-related disorder

Also linked: pulmonary fibrosis Adams-Oliver syndrome 3 dyskeratosis congenita, autosomal recessive 5 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 dyskeratosis congenita dyskeratosis congenita, autosomal dominant 4

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-arg986ter (accessed [today's date]).

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