Is TERT p.Leu706= (c.2118G>A) pathogenic?

TERT p.Leu706= (c.2118G>A) is classified Likely benign in TERT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-17). Very rare (popmax 0.009%, amr); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Leu706= (c.2118G>A)?

TERT p.Leu706= (c.2118G>A) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Leu706= (c.2118G>A) in the general population?

TERT p.Leu706= (c.2118G>A) is very rare (popmax 0.009%, amr) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

TERT p.Leu706=

c.2118G>A · rs377030225 · VCV416286

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.009%, amr)

Conditions

idiopathic pulmonary fibrosis

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 -0.55	GERP -2.5, phastCons 0.016
Overall
CADD	0.795	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.009% Admixed American · 5/55,544 alleles

Filtering AF 0.00415% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00436% 69/1,582,840 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.009%	11,109
European (non-Finnish)	0.00523%	19,128
African / African-American	0.00269%	37,143
Remaining individualsnot grpmax-eligible	0.00163%	61,228

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.Leu706=
Coding: c.2118G>A
MANE Select: NM_198253
dbSNP: rs377030225
Type: single nucleotide variant
Location: chr5:1279303 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 706: the reverse transcriptase domain; an α-helix

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

Disease context

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

Also linked: dyskeratosis congenita, autosomal dominant 2 dyskeratosis congenita

For Idiopathic pulmonary fibrosis (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

TERT c.2130+1G>A Likely pathogenic ★★ same condition
TERT c.2130+2T>G Likely pathogenic ★★ same condition
TERT c.2131-2A>G Likely pathogenic ★★ same condition
TERT c.2286+1G>A Likely pathogenic ★★ same condition
TERT c.3157+1G>T Likely pathogenic ★★ same condition
TERT p.Ala1009Val Likely pathogenic ★★ same condition
TERT p.Ala716Thr Pathogenic/Likely pathogenic ★★ same condition
TERT p.Ala716Val Pathogenic/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-leu706 (accessed [today's date]).

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