Is RTEL1 p.Ser1073= (c.3219C>T) pathogenic?

RTEL1 p.Ser1073= (c.3219C>T) is classified Likely benign in RTEL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-16). Ultra-rare (popmax 0.0312%, eas); Associated with Inborn genetic diseases.

How common is RTEL1 p.Ser1073= (c.3219C>T) in the general population?

RTEL1 p.Ser1073= (c.3219C>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

RTEL1 p.Ser1073=

Q: What condition is associated with RTEL1 p.Ser1073= (c.3219C>T)?

RTEL1 p.Ser1073= (c.3219C>T) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal recessive 5, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (ClinVar).

c.3219C>T · rs376151757 · VCV473919

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

Inborn genetic diseases

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 -7.8	GERP -1.5
Overall
CADD	3.775	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,888 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00471% 76/1,612,478 alleles · ultra-rare exomes 69/1,460,306 · genomes 7/152,172 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
South Asian	0.00988%	10,120
European (non-Finnish)	0.00348%	28,776
Remaining individualsnot grpmax-eligible	0.0032%	31,223
Admixed American	0.00167%	60,004
African / African-American	0.00133%	74,934

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.Ser1073=
Coding: c.3219C>T
MANE Select: NM_001283009
dbSNP: rs376151757
Type: single nucleotide variant
Location: chr20:63694850 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64 · 3 PDB
Residue 1073: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

RTEL1 p.Ser1073Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
RTEL1 p.Ser1073Phe Uncertain significance ★ ⚠ same residue
RTEL1 p.Ser1073Thr 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-ser1073 (accessed [today's date]).

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