TERT p.Arg643=
c.1927A>C · rs1749921453 · VCV1782784
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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 0.7 | GERP 1.2, phastCons 0.5 |
| Overall | ||
| CADD | 4.734 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TERT
- Protein
- p.Arg643=
- Coding
- c.1927A>C
- MANE Select
- NM_198253
- dbSNP
- rs1749921453
- Type
- single nucleotide variant
- Location
- chr5:1280181 (GRCh38)
- Gene constraint
- LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.98 · 32 PDB
- Residue 643
- the reverse transcriptase domain
Disease context
dyskeratosis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 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.Arg643Gly 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-arg643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown