Is TERT p.Arg381= (c.1143C>T) pathogenic?

TERT p.Arg381= (c.1143C>T) is classified Likely benign in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). Very rare (popmax 0.00164%, nfe); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Arg381= (c.1143C>T)?

TERT p.Arg381= (c.1143C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Arg381= (c.1143C>T) in the general population?

TERT p.Arg381= (c.1143C>T) is very rare (popmax 0.00164%, nfe) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Arg381=

c.1143C>T · rs878855298 · VCV242212

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00164%, nfe)

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 0.3	GERP 4.2, phastCons 0.96
Overall
CADD	5.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00164% European (non-Finnish) · 19/1,155,298 alleles

Filtering AF 0.00105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000848%

Overall 0.00149% 21/1,413,034 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0033%	30,346
European (non-Finnish)grpmax	0.00164%	60,805

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg381=
Coding: c.1143C>T
MANE Select: NM_198253
dbSNP: rs878855298
Type: single nucleotide variant
Location: chr5:1293743 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 381: an α-helix; a UniProt-annotated variant site (in); the 'required for oligomerization' region; the 'rna-interacting domain 2' region; the 'qfp motif' 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.Arg381Gly Uncertain significance ★★ ⚠ same residue
TERT p.Arg381His Uncertain significance ★★ ⚠ same residue
TERT p.Arg381Pro Uncertain significance ★★ ⚠ same residue
TERT p.Arg381Leu Uncertain significance ★ ⚠ same residue
TERT p.Arg381fs Pathogenic ★ same residue
TERT p.Arg381Cys Uncertain significance ★ ⚠ same residue
TERT c.2130+1G>A Likely pathogenic ★★ same condition
TERT c.2130+2T>G 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-arg381 (accessed [today's date]).

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