Is TERT p.Val747fs (c.2240del) pathogenic?

TERT p.Val747fs (c.2240del) is classified Pathogenic in TERT (ClinVar, Single submitter, 4 submitters; last evaluated 2019-11-19). Absent from gnomAD; Associated with pulmonary fibrosis.

What condition is associated with TERT p.Val747fs (c.2240del)?

TERT p.Val747fs (c.2240del) is associated with pulmonary fibrosis, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1, interstitial lung disease 2 (ClinVar).

How common is TERT p.Val747fs (c.2240del) in the general population?

TERT p.Val747fs (c.2240del) is absent from gnomAD (gnomAD).

TERT p.Val747fs

c.2240del · rs199422300 · VCV12737

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pulmonary fibrosis

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 6 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.015	GERP -2.2, phastCons 0.65

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.Val747fs
Coding: c.2240del
MANE Select: NM_198253
dbSNP: rs199422300
Type: Deletion
Location: chr5:1278687 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 747: the reverse transcriptase domain; a β-strand

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

Disease context

pulmonary fibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 interstitial lung disease 2

Similar variants

TERT p.Cys998fs Pathogenic/Likely pathogenic ★★ same condition
TERT p.Val747Ile Uncertain significance ★★ ⚠ same residue
TERT p.Val747= Likely benign ★★ same residue
TERT p.Asp685del Pathogenic ★ same condition
TERT p.Phe809fs Likely pathogenic ★ same condition
TERT p.Val461_Tyr462insTer Pathogenic ★ same condition
TERT p.Val747Ala Uncertain significance ★ ⚠ same residue
TERT c.*6_*182del 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-val747fs (accessed [today's date]).

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