Is TERT p.Pro233Arg (c.698C>G) pathogenic?

TERT p.Pro233Arg (c.698C>G) is classified Uncertain significance in TERT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-03). AlphaMissense: likely benign (0.1126); Very rare (popmax 0.00113%, sas); Associated with dyskeratosis congenita.

What condition is associated with TERT p.Pro233Arg (c.698C>G)?

TERT p.Pro233Arg (c.698C>G) is associated with dyskeratosis congenita (ClinVar).

How common is TERT p.Pro233Arg (c.698C>G) in the general population?

TERT p.Pro233Arg (c.698C>G) is very rare (popmax 0.00113%, sas) (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about TERT p.Pro233Arg (c.698C>G)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

TERT p.Pro233Arg

c.698C>G · VCV4841363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 6.3, phastCons 0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.082 · regional, not allelic
Overall
CADD	19.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,526 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00021% 3/1,429,286 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00113%	88,526
European (non-Finnish)	0.000171%	584,153

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.Pro233Arg
Coding: c.698C>G
MANE Select: NM_198253
Type: single nucleotide variant
Location: chr5:1294188 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 233: 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

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.Pro233Leu Uncertain significance ★★ ⚠ same residue
TERT p.Pro233= Likely benign ★★ same residue
TERT p.Pro233Gln 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

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-pro233arg (accessed [today's date]).

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