Is TERT p.Pro1121= (c.3363G>A) pathogenic?

TERT p.Pro1121= (c.3363G>A) is classified Likely benign in TERT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.0227%, afr); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Pro1121= (c.3363G>A)?

TERT p.Pro1121= (c.3363G>A) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Pro1121= (c.3363G>A) in the general population?

TERT p.Pro1121= (c.3363G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Pro1121=

c.3363G>A · rs750020682 · VCV471889

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, 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 -20	GERP -2.2
Overall
CADD	0.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,928 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00267% 43/1,612,080 alleles · ultra-rare exomes 33/1,459,872 · genomes 10/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,408
Finnishnot grpmax-eligible	0.0175%	5,721
Remaining individualsnot grpmax-eligible	0.00801%	12,484
East Asian	0.00223%	44,882
European (non-Finnish)	0.000763%	131,092

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.Pro1121=
Coding: c.3363G>A
MANE Select: NM_198253
dbSNP: rs750020682
Type: single nucleotide variant
Location: chr5:1253764 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 1121: the 'cte' region; a β-strand

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 p.Pro1121Ala Uncertain significance ★★ ⚠ same residue
TERT p.Pro1121Arg Uncertain significance ★ ⚠ same residue
TERT p.Pro1121Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT p.Pro1121Thr 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-pro1121 (accessed [today's date]).

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