Is TERT p.Asp848fs (c.2540dup) pathogenic?

TERT p.Asp848fs (c.2540dup) is classified Pathogenic in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-12). Absent from gnomAD; Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Asp848fs (c.2540dup)?

TERT p.Asp848fs (c.2540dup) is associated with dyskeratosis congenita, autosomal dominant 2, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Asp848fs (c.2540dup) in the general population?

TERT p.Asp848fs (c.2540dup) is absent from gnomAD (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TERT p.Asp848fs

c.2540dup · rs1748786633 · VCV841032

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dyskeratosis congenita, autosomal dominant 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7	GERP -2.2

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TERT
Protein: p.Asp848fs
Coding: c.2540dup
MANE Select: NM_198253
dbSNP: rs1748786633
Type: Duplication
Location: chr5:1268561 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 848: the reverse transcriptase domain; an α-helix

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

Disease context

dyskeratosis congenita, autosomal dominant 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: idiopathic pulmonary fibrosis

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TERT p.Asp848Asn Uncertain significance ★★ ⚠ same residue
TERT p.Asp848= Likely benign ★★ same residue
TERT c.2655-47_2659dup Uncertain significance ★★ same condition
TERT p.Cys271fs Pathogenic ★ same condition
TERT p.His205fs Pathogenic ★ same condition
TERT p.Pro625fs Pathogenic ★ same condition
TERT p.Ser309fs Pathogenic ★ same condition
TERT p.Pro174_Thr182dup Uncertain significance ★ 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/tert-p-asp848fs (accessed [today's date]).

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