Is DSPP p.Asn646fs (c.1937del) pathogenic?

DSPP p.Asn646fs (c.1937del) is classified Pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Associated with Dentin dysplasia, Type II; DTDP2.

What condition is associated with DSPP p.Asn646fs (c.1937del)?

DSPP p.Asn646fs (c.1937del) is associated with Dentin dysplasia, Type II; DTDP2 (ClinVar).

DSPP p.Asn646fs

c.1937del · VCV4082230

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Dentin dysplasia, Type II; DTDP2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -8	GERP -1.8
Region caveats
Repeat context	tandem	(CAGTGA)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Variant & gene context

Gene: DSPP
Protein: p.Asn646fs
Coding: c.1937del
Type: Deletion
Location: chr4:87614598 (GRCh38)

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

Disease context

Dentin dysplasia, Type II; DTDP2

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-asn646fs (accessed [today's date]).

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