Is TERT p.Asp628= (c.1884C>T) pathogenic?

TERT p.Asp628= (c.1884C>T) is classified Benign/Likely benign in TERT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-16). Rare (popmax 0.29%, afr); Associated with dyskeratosis congenita.

What condition is associated with TERT p.Asp628= (c.1884C>T)?

TERT p.Asp628= (c.1884C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal dominant 2, melanoma, cutaneous malignant, susceptibility to, 9 (ClinVar).

How common is TERT p.Asp628= (c.1884C>T) in the general population?

TERT p.Asp628= (c.1884C>T) is rare (popmax 0.29%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

TERT p.Asp628=

c.1884C>T · rs143992655 · VCV436979

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.29%, afr)

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 -5.3	GERP -2.5
Overall
CADD	1.619	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.29% African / African-American · 218/75,078 alleles

Filtering AF 0.259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.247%

Overall 0.0198% 320/1,613,982 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.29%	344
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.0233%	4,288
South Asian	0.0143%	7,007
European (non-Finnish)	0.00475%	21,072
East Asian	0.00223%	44,892

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.Asp628=
Coding: c.1884C>T
MANE Select: NM_198253
dbSNP: rs143992655
Type: single nucleotide variant
Location: chr5:1280224 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.98 · 32 PDB
Residue 628: the reverse transcriptase domain

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

Also linked: dyskeratosis congenita, autosomal dominant 2 melanoma, cutaneous malignant, susceptibility to, 9 acute myeloid leukemia 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.Asp628Asn Uncertain significance ★ ⚠ same residue
TERT p.Asp628Gly 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
TERT p.Ala1009Val 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-asp628 (accessed [today's date]).

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