Is TERT p.Pro614= (c.1842C>T) pathogenic?

TERT p.Pro614= (c.1842C>T) is classified Likely benign in TERT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0133%, afr); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Pro614= (c.1842C>T)?

TERT p.Pro614= (c.1842C>T) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Pro614= (c.1842C>T) in the general population?

TERT p.Pro614= (c.1842C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TERT p.Pro614=

c.1842C>T · rs747157175 · VCV706284

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

dyskeratosis congenita, autosomal dominant 2

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 -13	GERP -2.4
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,940 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00174% 28/1,613,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,494
Admixed American	0.0117%	8,573
East Asian	0.00668%	14,965
South Asian	0.0022%	45,545
European (non-Finnish)	0.000508%	196,671

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.Pro614=
Coding: c.1842C>T
MANE Select: NM_198253
dbSNP: rs747157175
Type: single nucleotide variant
Location: chr5:1280266 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 614: the reverse transcriptase domain; a β-strand

Full TERT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyskeratosis congenita, autosomal dominant 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita idiopathic pulmonary fibrosis

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TERT p.Pro614His Uncertain significance ★★ ⚠ same residue
TERT p.Pro614Ala Uncertain significance ★ ⚠ same residue
TERT p.Pro614Ser 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

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-pro614 (accessed [today's date]).

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