Is TERT p.Ser579Arg (c.1737T>A) pathogenic?

TERT p.Ser579Arg (c.1737T>A) is classified Conflicting classifications of pathogenicity in TERT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.1892); Very rare (popmax 8.47e-05%, nfe); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Ser579Arg (c.1737T>A)?

TERT p.Ser579Arg (c.1737T>A) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Ser579Arg (c.1737T>A) in the general population?

TERT p.Ser579Arg (c.1737T>A) is very rare (popmax 8.47e-05%, nfe) (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.Ser579Arg (c.1737T>A)?

AlphaMissense predicts likely benign (score 0.1892) — an in-silico prediction, not a clinical call.

TERT p.Ser579Arg

c.1737T>A · rs1395379702 · VCV648158

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic pulmonary fibrosis

Computational evidence

Protein change
AlphaMissense	0.1892	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -1.1
Regional constraint	o/e 0.58	unconstrained · MANE · 29 kb · p 2.3e-32 · regional, not allelic
Overall
CADD	2.306	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,948 alleles

Overall 0.000658% 1/151,864 alleles · very rare

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.Ser579Arg
Coding: c.1737T>A
MANE Select: NM_198253
dbSNP: rs1395379702
Type: single nucleotide variant
Location: chr5:1282461 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 579: 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 dyskeratosis congenita

For Idiopathic pulmonary fibrosis (Orphanet):

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

Similar variants

TERT p.Ser579Ile Uncertain significance ★★ ⚠ same residue
TERT p.Ser579= Likely benign ★★ same residue
TERT p.Ser579Asn Uncertain significance ★ ⚠ same residue
TERT p.Ser579Cys 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-ser579arg (accessed [today's date]).

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