Is TERT p.Pro250= (c.750C>T) pathogenic?

TERT p.Pro250= (c.750C>T) is classified Likely benign in TERT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-12). Ultra-rare (popmax 0.0166%, mid); Associated with dyskeratosis congenita.

What condition is associated with TERT p.Pro250= (c.750C>T)?

TERT p.Pro250= (c.750C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal dominant 2, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.Pro250= (c.750C>T) in the general population?

TERT p.Pro250= (c.750C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Pro250=

c.750C>T · rs761741087 · VCV1141179

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2	GERP -5.3
Overall
CADD	2.346	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,034 alleles

Filtering AF 0.000774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00037%

Overall 0.00101% 16/1,581,966 alleles · ultra-rare exomes 16/1,429,622 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,034
East Asian	0.00467%	21,409
African / African-American	0.00269%	37,121
European (non-Finnish)	0.000943%	106,047

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.Pro250=
Coding: c.750C>T
MANE Select: NM_198253
dbSNP: rs761741087
Type: single nucleotide variant
Location: chr5:1294136 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 250: the 'disordered' region; the 'linker' region

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

Disease context

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

Also linked: dyskeratosis congenita, autosomal dominant 2 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.Pro250Leu 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
TERT p.Ala716Thr 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-pro250 (accessed [today's date]).

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