Is DSPP p.Ser1204fs (c.3611del) pathogenic?

DSPP p.Ser1204fs (c.3611del) is classified Likely pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-28). Absent from gnomAD; Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Ser1204fs (c.3611del)?

DSPP p.Ser1204fs (c.3611del) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Ser1204fs (c.3611del) in the general population?

DSPP p.Ser1204fs (c.3611del) is absent from gnomAD (gnomAD).

How is Dentinogenesis imperfecta inherited?

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

DSPP p.Ser1204fs

c.3611del · rs2109999064 · VCV1299353

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP 1.6, phastCons 0.004
Region caveats
Repeat context	tandem	GATAGCAGT simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSPP
Protein: p.Ser1204fs
Coding: c.3611del
MANE Select: NM_014208
dbSNP: rs2109999064
Type: Deletion
Location: chr4:87616273 (GRCh38)
Gene constraint: LOEUF 1.271 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 39.36
Residue 1204: the 'disordered' region

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)

Similar variants

DSPP p.Ser1180fs Pathogenic ★ same condition
DSPP p.Ser945fs Likely pathogenic same condition
DSPP p.Glu327Asp Uncertain significance ★★ ⚠ same condition
DSPP p.Glu511Ter Likely pathogenic ★ same condition
DSPP p.Glu47Lys Conflicting classifications of pathogenicity ★ ⚠ 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/dspp-p-ser1204fs (accessed [today's date]).

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