Is TERT p.Ala531= (c.1593C>T) pathogenic?

TERT p.Ala531= (c.1593C>T) is classified Likely benign in TERT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-17). Ultra-rare (popmax 0.0143%, sas); Associated with idiopathic pulmonary fibrosis.

What condition is associated with TERT p.Ala531= (c.1593C>T)?

TERT p.Ala531= (c.1593C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita (ClinVar).

How common is TERT p.Ala531= (c.1593C>T) in the general population?

TERT p.Ala531= (c.1593C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Ala531=

c.1593C>T · rs146462061 · VCV697661

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Conditions

idiopathic pulmonary fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.9	GERP -12
Overall
CADD	0.353	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,086 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00211% 34/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,007
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)	0.00161%	62,106

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.Ala531=
Coding: c.1593C>T
MANE Select: NM_198253
dbSNP: rs146462061
Type: single nucleotide variant
Location: chr5:1282605 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 531: an α-helix; 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 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
TERT p.Ala716Val 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-ala531 (accessed [today's date]).

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