Is TERT p.Pro370= (c.1110C>G) pathogenic?

TERT p.Pro370= (c.1110C>G) is classified Likely benign in TERT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-11). Very rare (popmax 0.00241%, eas); Associated with dyskeratosis congenita, autosomal dominant 2.

What condition is associated with TERT p.Pro370= (c.1110C>G)?

TERT p.Pro370= (c.1110C>G) is associated with dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 1, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 (ClinVar).

How common is TERT p.Pro370= (c.1110C>G) in the general population?

TERT p.Pro370= (c.1110C>G) is very rare (popmax 0.00241%, eas) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Pro370=

c.1110C>G · rs1579597009 · VCV758712

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00241%, eas)

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 -1.1	GERP -0.54
Overall
CADD	1.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00241% East Asian · 1/41,492 alleles

Overall 6.43e-05% 1/1,554,104 alleles · very rare exomes 1/1,401,758 · genomes 0/152,346 · joint denominator

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.Pro370=
Coding: c.1110C>G
MANE Select: NM_198253
dbSNP: rs1579597009
Type: single nucleotide variant
Location: chr5:1293776 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 370: 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

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

Also linked: dyskeratosis congenita, autosomal dominant 1 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 melanoma, cutaneous malignant, susceptibility to, 9 dyskeratosis congenita aplastic anemia acute myeloid leukemia interstitial lung disease 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.Pro370Ser Uncertain significance ★★ ⚠ same residue
TERT p.Pro370Arg Uncertain significance ★ ⚠ same residue
TERT p.Pro370His 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-pro370 (accessed [today's date]).

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