Is TERT p.His752= (c.2256T>C) pathogenic?

TERT p.His752= (c.2256T>C) is classified Likely benign in TERT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0243%, nfe); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.His752= (c.2256T>C)?

TERT p.His752= (c.2256T>C) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, idiopathic pulmonary fibrosis (ClinVar).

How common is TERT p.His752= (c.2256T>C) in the general population?

TERT p.His752= (c.2256T>C) is ultra-rare (popmax 0.0243%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.His752=

c.2256T>C · rs745650751 · VCV263105

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, nfe)

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 -4.5	GERP -2.2
Overall
CADD	1.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0243% European (non-Finnish) · 287/1,180,026 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.0186% 300/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0243%	4,112
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00267%	37,465
South Asian	0.0022%	45,546
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	63,946

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.His752=
Coding: c.2256T>C
MANE Select: NM_198253
dbSNP: rs745650751
Type: single nucleotide variant
Location: chr5:1278671 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 752: the reverse transcriptase domain

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.His752Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
TERT p.His752Asp Uncertain significance ★ ⚠ same residue
TERT p.His752Tyr 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-his752 (accessed [today's date]).

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