Is TERT p.Pro44Leu (c.131C>T) pathogenic?

TERT p.Pro44Leu (c.131C>T) is classified Uncertain significance in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-18). AlphaMissense: ambiguous (0.3587); No allele count reported in gnomAD v4.1 (AN 1,456,834); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Pro44Leu (c.131C>T)?

TERT p.Pro44Leu (c.131C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Pro44Leu (c.131C>T) in the general population?

TERT p.Pro44Leu (c.131C>T) is no allele count reported in gnomAD v4.1 (AN 1,456,834) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

What do computational predictors say about TERT p.Pro44Leu (c.131C>T)?

AlphaMissense predicts ambiguous (score 0.3587) — an in-silico prediction, not a clinical call.

TERT p.Pro44Leu

c.131C>T · rs2126691833 · VCV1403439

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3587 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,456,834)

Conditions

idiopathic pulmonary fibrosis

Computational evidence

Protein change
AlphaMissense	0.3587	ambiguous
REVEL	0.557	indeterminate
SaProt	LLR -11.65	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 7.2, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 380 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,456,834). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TERT
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_198253
dbSNP: rs2126691833
Type: single nucleotide variant
Location: chr5:1294859 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 44: the 'rna-interacting domain 1' region

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.Pro44= Likely benign ★★ 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
TERT p.Ala1009Val Likely pathogenic ★★ same condition
TERT p.Ala716Thr 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-pro44leu (accessed [today's date]).

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