Is TERT p.Phe464= (c.1392C>T) pathogenic?

TERT p.Phe464= (c.1392C>T) is classified Benign/Likely benign in TERT (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-26). Rare (popmax 0.837%, sas); Associated with idiopathic pulmonary fibrosis.

How common is TERT p.Phe464= (c.1392C>T) in the general population?

TERT p.Phe464= (c.1392C>T) is rare (popmax 0.837%, sas) (gnomAD).

How is Idiopathic pulmonary fibrosis inherited?

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

TERT p.Phe464=

Q: What condition is associated with TERT p.Phe464= (c.1392C>T)?

TERT p.Phe464= (c.1392C>T) is associated with idiopathic pulmonary fibrosis, dyskeratosis congenita, autosomal dominant 2, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

c.1392C>T · rs186596886 · VCV242217

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.837%, sas)

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 -0.011	GERP 1.8, phastCons 0.2
Overall
CADD	3.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.837% South Asian · 737/88,086 alleles

Filtering AF 0.787% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.767%

Overall 0.0543% 862/1,587,594 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.837%	120
Middle Eastern	0.199%	502
Remaining individualsnot grpmax-eligible	0.0667%	1,499
Ashkenazi Jewishnot grpmax-eligible	0.031%	3,229
European (non-Finnish)	0.00514%	19,464
East Asian	0.00231%	43,362
Admixed American	0.00179%	55,856
African / African-American	0.00134%	74,508

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.Phe464=
Coding: c.1392C>T
MANE Select: NM_198253
dbSNP: rs186596886
Type: single nucleotide variant
Location: chr5:1293494 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 464: an α-helix; 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 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 melanoma, cutaneous malignant, susceptibility to, 9 dyskeratosis congenita aplastic anemia acute myeloid leukemia

For Idiopathic pulmonary fibrosis (Orphanet):

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

Similar variants

TERT p.Phe464Leu Uncertain significance ★★ ⚠ same residue
TERT p.Phe464Ile 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
TERT c.3157+1G>T Likely pathogenic ★★ same condition
TERT p.Ala1009Val 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-phe464 (accessed [today's date]).

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