Is TERT p.Ser334= (c.1002C>T) pathogenic?

TERT p.Ser334= (c.1002C>T) is classified Likely benign in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-12). Very rare (popmax 0.000262%, nfe); Associated with dyskeratosis congenita.

What condition is associated with TERT p.Ser334= (c.1002C>T)?

TERT p.Ser334= (c.1002C>T) is associated with dyskeratosis congenita (ClinVar).

How common is TERT p.Ser334= (c.1002C>T) in the general population?

TERT p.Ser334= (c.1002C>T) is very rare (popmax 0.000262%, 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.Ser334=

c.1002C>T · rs1561213888 · VCV2454087

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000262%, nfe)

Conditions

dyskeratosis congenita

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 0.73	GERP 3.1, phastCons 0.17
Overall
CADD	2.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000262% European (non-Finnish) · 3/1,146,978 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000259% 4/1,543,596 alleles · very rare exomes 4/1,391,304 · genomes 0/152,292 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,068
European (non-Finnish)grpmax	0.000262%	382,326

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser334=
Coding: c.1002C>T
MANE Select: NM_198253
dbSNP: rs1561213888
Type: single nucleotide variant
Location: chr5:1293884 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 334: 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 — 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.Ser334Phe 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-ser334 (accessed [today's date]).

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