Is TERT p.Ala699= (c.2097C>T) pathogenic?

TERT p.Ala699= (c.2097C>T) is classified Benign in TERT (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Common (popmax 5.11%, eas) — too common for a highly-penetrant pathogenic allele; Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Ala699= (c.2097C>T)?

TERT p.Ala699= (c.2097C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 1, dyskeratosis congenita, autosomal dominant 2 (ClinVar).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Ala699=

Q: How common is TERT p.Ala699= (c.2097C>T) in the general population?

TERT p.Ala699= (c.2097C>T) is common (popmax 5.11%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2097C>T · rs33963617 · VCV39107

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Common

common (popmax 5.11%, eas) — too common for a highly-penetrant pathogenic allele

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 0.12	GERP -2.5, phastCons 0.003
Overall
CADD	3.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.11% East Asian · 2,216/43,398 alleles

Filtering AF 4.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.86%

Overall 0.899% 14,255/1,585,702 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.11%	20
Amishnot grpmax-eligible	1.32%	76
Remaining individualsnot grpmax-eligible	1.07%	94
European (non-Finnish)	0.86%	116
Ashkenazi Jewishnot grpmax-eligible	0.718%	139
South Asian	0.646%	155
Finnishnot grpmax-eligible	0.351%	285
Admixed American	0.35%	286
Middle Eastern	0.201%	498
African / African-American	0.185%	540

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.Ala699=
Coding: c.2097C>T
MANE Select: NM_198253
dbSNP: rs33963617
Type: single nucleotide variant
Location: chr5:1279324 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 699: the reverse transcriptase domain

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

For Idiopathic pulmonary fibrosis (Orphanet):

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

Similar variants

TERT p.Ala699Thr Uncertain significance ★★ ⚠ same residue
TERT p.Ala699Ser Uncertain significance ★ ⚠ same residue
TERT p.Ala699Val Uncertain significance ★ ⚠ same residue
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

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-ala699 (accessed [today's date]).

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