Is TERT p.Ser504= (c.1512G>T) pathogenic?

TERT p.Ser504= (c.1512G>T) is classified Likely benign in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). Very rare (popmax 6.2e-05%); Associated with dyskeratosis congenita.

What condition is associated with TERT p.Ser504= (c.1512G>T)?

TERT p.Ser504= (c.1512G>T) is associated with dyskeratosis congenita (ClinVar).

How common is TERT p.Ser504= (c.1512G>T) in the general population?

TERT p.Ser504= (c.1512G>T) is very rare (popmax 6.2e-05%) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Ser504=

c.1512G>T · rs779846566 · VCV1774249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 -13	GERP -14
Overall
CADD	0.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,386 alleles · very rare exomes 1/1,461,004 · genomes 0/152,382 · 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.Ser504=
Coding: c.1512G>T
MANE Select: NM_198253
dbSNP: rs779846566
Type: single nucleotide variant
Location: chr5:1293374 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 504: a β-strand; 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

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

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.Ser504Trp Uncertain significance ★★ same residue
TERT c.2286+1G>A Likely pathogenic ★★ same condition
TERT p.Ala716Val Pathogenic/Likely pathogenic ★★ same condition
TERT p.Arg230Ter Pathogenic ★★ same condition
TERT p.Arg631Gln Pathogenic ★★ same condition
TERT p.Arg631Trp Pathogenic/Likely pathogenic ★★ same condition
TERT p.Arg671Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TERT p.Arg865His 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-ser504 (accessed [today's date]).

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