Is TERT p.Pro308fs (c.923del) pathogenic?

TERT p.Pro308fs (c.923del) is classified Pathogenic in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-11). Very rare (popmax 8.67e-05%, nfe); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Pro308fs (c.923del)?

TERT p.Pro308fs (c.923del) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Pro308fs (c.923del) in the general population?

TERT p.Pro308fs (c.923del) is very rare (popmax 8.67e-05%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Pro308fs

c.923del · rs1191885727 · VCV2928164

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.67e-05%, nfe)

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 2 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6	GERP -4.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.67e-05% European (non-Finnish) · 1/1,153,254 alleles

Overall 7.13e-05% 1/1,402,912 alleles · very rare

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: TERT
Protein: p.Pro308fs
Coding: c.923del
MANE Select: NM_198253
dbSNP: rs1191885727
Type: Deletion
Location: chr5:1293963 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 308: the 'disordered' region; the 'linker' region; the 'required for oligomerization' region

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: dyskeratosis congenita 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.Pro308Ala Uncertain significance ★★ ⚠ same residue
TERT p.Pro308Leu Uncertain significance ★ ⚠ same residue
TERT p.Pro308Ser Uncertain significance ★ ⚠ same residue
TERT p.Pro308= Likely benign ★ same residue
TERT p.Arg821fs Pathogenic/Likely pathogenic ★★ same condition
TERT p.Leu392fs Pathogenic ★★ same condition
TERT p.Tyr333fs Pathogenic/Likely pathogenic ★★ same condition
TERT c.(?_1574 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/tert-p-pro308fs (accessed [today's date]).

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