Is TERT p.Cys982= (c.2946T>C) pathogenic?

TERT p.Cys982= (c.2946T>C) is classified Likely benign in TERT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-22). Rare (popmax 0.241%, eas); Associated with idiopathic pulmonary fibrosis.

How common is TERT p.Cys982= (c.2946T>C) in the general population?

TERT p.Cys982= (c.2946T>C) is rare (popmax 0.241%, eas) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Cys982=

Q: What condition is associated with TERT p.Cys982= (c.2946T>C)?

TERT p.Cys982= (c.2946T>C) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

c.2946T>C · rs201689770 · VCV242233

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.241%, eas)

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 0.53	GERP -2.1, phastCons 0.96
Overall
CADD	7.357	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.241% East Asian · 108/44,886 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.00743% 120/1,614,156 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.241%	416
Remaining individualsnot grpmax-eligible	0.0048%	20,837
South Asian	0.0022%	45,540
European (non-Finnish)	0.000593%	168,570

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.Cys982=
Coding: c.2946T>C
MANE Select: NM_198253
dbSNP: rs201689770
Type: single nucleotide variant
Location: chr5:1260498 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 982: the 'cte' region; 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 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 dyskeratosis congenita aplastic anemia

For Idiopathic pulmonary fibrosis (Orphanet):

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

Similar variants

TERT p.Cys982Phe Uncertain significance ★★ ⚠ same residue
TERT p.Cys982Arg Uncertain significance ★ ⚠ same residue
TERT p.Cys982Ser Uncertain significance ★ ⚠ same residue
TERT p.Cys982Tyr 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

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-cys982 (accessed [today's date]).

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