Is RTEL1 p.Val956= (c.2868G>A) pathogenic?

RTEL1 p.Val956= (c.2868G>A) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-06). Ultra-rare (popmax 0.0329%, mid); Associated with dyskeratosis congenita, autosomal recessive 5.

What condition is associated with RTEL1 p.Val956= (c.2868G>A)?

RTEL1 p.Val956= (c.2868G>A) is associated with dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

How common is RTEL1 p.Val956= (c.2868G>A) in the general population?

RTEL1 p.Val956= (c.2868G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

RTEL1 p.Val956=

c.2868G>A · rs766435400 · VCV1641048

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -1.4, phastCons 0.98
Overall
CADD	6.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000248% 4/1,612,068 alleles · ultra-rare exomes 3/1,459,976 · genomes 1/152,092 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
European (non-Finnish)	0.00017%	589,786

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.Val956=
Coding: c.2868G>A
MANE Select: NM_001283009
dbSNP: rs766435400
Type: single nucleotide variant
Location: chr20:63693159 (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.Val956Leu Uncertain significance ★★ ⚠ same residue
RTEL1 p.Val956fs Pathogenic ★ same residue
RTEL1 p.Val956Gly 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-val956 (accessed [today's date]).

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