Is TERT p.Pro524Ser (c.1570C>T) pathogenic?

TERT p.Pro524Ser (c.1570C>T) is classified Uncertain significance in TERT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-10). AlphaMissense: likely benign (0.1048); Absent from gnomAD v4.1; Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Pro524Ser (c.1570C>T)?

TERT p.Pro524Ser (c.1570C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Pro524Ser (c.1570C>T) in the general population?

TERT p.Pro524Ser (c.1570C>T) is absent from gnomAD v4.1 (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.Pro524Ser (c.1570C>T)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

TERT p.Pro524Ser

c.1570C>T · rs898648592 · VCV1381857

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

idiopathic pulmonary fibrosis

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 6.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.082 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TERT
Protein: p.Pro524Ser
Coding: c.1570C>T
MANE Select: NM_198253
dbSNP: rs898648592
Type: single nucleotide variant
Location: chr5:1293316 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 524: a β-strand; the 'required for oligomerization' region; the 'rna-interacting domain 2' 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.Pro524Gln Uncertain significance ★★ ⚠ same residue
TERT p.Pro524Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT p.Pro524Arg Uncertain significance ★ ⚠ same residue
TERT p.Pro524Thr 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-pro524ser (accessed [today's date]).

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