Is RTEL1 p.Lys897Asn (c.2691G>T) pathogenic?

RTEL1 p.Lys897Asn (c.2691G>T) is classified Uncertain significance in RTEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-03). AlphaMissense: ambiguous (0.531); Absent from gnomAD v4.1.

How common is RTEL1 p.Lys897Asn (c.2691G>T) in the general population?

RTEL1 p.Lys897Asn (c.2691G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RTEL1 p.Lys897Asn (c.2691G>T)?

AlphaMissense predicts ambiguous (score 0.531) — an in-silico prediction, not a clinical call.

RTEL1 p.Lys897Asn

c.2691G>T · VCV4945870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.531 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.531	ambiguous
REVEL	0.091	moderately benign-leaning
SaProt	LLR -3.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.22, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 5,558 bp · p 3.7e-34 · regional, not allelic
Overall
CADD	21.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RTEL1
Protein: p.Lys897Asn
Coding: c.2691G>T
MANE Select: NM_001283009
Type: single nucleotide variant
Location: chr20:63692843 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 897: a UniProt-annotated variant site (in dkcb5; severe form consistent with hoyeraal-hreidarsson syndrome)

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

Similar variants

RTEL1 p.Lys897Arg Uncertain significance ★★ ⚠ same residue
RTEL1 c.1037+1G>T Likely pathogenic ★★ same type
RTEL1 c.1192-2A>G Likely pathogenic ★★ same type
RTEL1 c.1596-1G>A Likely pathogenic ★★ same type
RTEL1 c.2142-1G>C Likely pathogenic ★★ same type
RTEL1 c.2265+1G>T Likely pathogenic ★★ same type
RTEL1 c.2413+1G>A Likely pathogenic ★★ same type
RTEL1 c.2413+1G>C Pathogenic/Likely pathogenic ★★ same type

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-lys897asn (accessed [today's date]).

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