Is TERT p.Phe693= (c.2079C>T) pathogenic?

TERT p.Phe693= (c.2079C>T) is classified Likely benign in TERT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0309%, afr); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Phe693= (c.2079C>T)?

TERT p.Phe693= (c.2079C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 1, dyskeratosis congenita, autosomal dominant 2 (ClinVar).

How common is TERT p.Phe693= (c.2079C>T) in the general population?

TERT p.Phe693= (c.2079C>T) is ultra-rare (popmax 0.0309%, afr) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Phe693=

c.2079C>T · rs371759577 · VCV471849

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, afr)

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 -9.8	GERP -2.5
Overall
CADD	1.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0309% African / African-American · 23/74,406 alleles

Filtering AF 0.0211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00189% 30/1,584,410 alleles · ultra-rare exomes 13/1,432,112 · genomes 17/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0309%	3,235
Admixed American	0.00358%	27,935
Remaining individualsnot grpmax-eligible	0.00326%	30,635
East Asian	0.00231%	43,312
South Asian	0.0023%	43,419

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.Phe693=
Coding: c.2079C>T
MANE Select: NM_198253
dbSNP: rs371759577
Type: single nucleotide variant
Location: chr5:1279342 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 693: 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 1 dyskeratosis congenita, autosomal dominant 2 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 melanoma, cutaneous malignant, susceptibility to, 9 dyskeratosis congenita aplastic anemia acute myeloid leukemia interstitial lung disease 2

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-phe693 (accessed [today's date]).

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