Is DSPP p.Gln45Ter (c.133C>T) pathogenic?

DSPP p.Gln45Ter (c.133C>T) is classified Pathogenic in DSPP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2001-02-01). Absent from gnomAD v4.1; Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Gln45Ter (c.133C>T)?

DSPP p.Gln45Ter (c.133C>T) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Gln45Ter (c.133C>T) in the general population?

DSPP p.Gln45Ter (c.133C>T) is absent from gnomAD v4.1 (gnomAD).

How is Dentinogenesis imperfecta inherited?

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

DSPP p.Gln45Ter

c.133C>T · rs121912985 · VCV16853

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.60	loss · gain 0.03 · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: DSPP
Protein: p.Gln45Ter
Coding: c.133C>T
dbSNP: rs121912985
Type: single nucleotide variant
Location: chr4:87612186 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dentinogenesis imperfecta type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dentinogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-5 / 10 000 (Europe)

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/dspp-p-gln45ter (accessed [today's date]).

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