Is RTEL1 p.Ala1275= (c.3825C>T) pathogenic?

RTEL1 p.Ala1275= (c.3825C>T) is classified Conflicting classifications of pathogenicity in RTEL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-28). AlphaMissense: likely benign (0.0722); Very rare (popmax 0.00227%, eas); Associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3.

How common is RTEL1 p.Ala1275= (c.3825C>T) in the general population?

RTEL1 p.Ala1275= (c.3825C>T) is very rare (popmax 0.00227%, eas) (gnomAD).

What do computational predictors say about RTEL1 p.Ala1275= (c.3825C>T)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

RTEL1 p.Ala1275=

Q: What condition is associated with RTEL1 p.Ala1275= (c.3825C>T)?

RTEL1 p.Ala1275= (c.3825C>T) is associated with pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, dyskeratosis congenita, autosomal recessive 5 (ClinVar).

c.3825C>T · rs775014813 · VCV1572813

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.25	GERP -2.9
Overall
CADD	5.143	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 0.00227% East Asian · 1/43,974 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000503% 8/1,591,840 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00227%	43,974
South Asian	0.00113%	88,504
European (non-Finnish)	0.000513%	195,013

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.Ala1275=
Coding: c.3825C>T
dbSNP: rs775014813
Type: single nucleotide variant
Location: chr20:63695780 (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

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-ala1275 (accessed [today's date]).

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