Is DSPP p.Ser1001Arg (c.3003C>G) pathogenic?

DSPP p.Ser1001Arg (c.3003C>G) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-23). AlphaMissense: likely pathogenic (0.8023); Absent from gnomAD v4.1; Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Ser1001Arg (c.3003C>G)?

DSPP p.Ser1001Arg (c.3003C>G) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Ser1001Arg (c.3003C>G) in the general population?

DSPP p.Ser1001Arg (c.3003C>G) 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.

What do computational predictors say about DSPP p.Ser1001Arg (c.3003C>G)?

AlphaMissense predicts likely pathogenic (score 0.8023) — an in-silico prediction, not a clinical call.

DSPP p.Ser1001Arg

c.3003C>G · rs535605955 · VCV930250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8023 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
AlphaMissense	0.8023	likely pathogenic
REVEL	0.161	moderately benign-leaning
SaProt	LLR -12.51	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -1.3
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	9.886	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser1001Arg
Coding: c.3003C>G
dbSNP: rs535605955
Type: single nucleotide variant
Location: chr4:87615665 (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-ser1001arg (accessed [today's date]).

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