Is DSPP p.Val18Asp (c.53T>A) pathogenic?

DSPP p.Val18Asp (c.53T>A) is classified Likely pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). AlphaMissense: likely pathogenic (0.833); Absent from gnomAD v4.1; Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Val18Asp (c.53T>A)?

DSPP p.Val18Asp (c.53T>A) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Val18Asp (c.53T>A) in the general population?

DSPP p.Val18Asp (c.53T>A) 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.Val18Asp (c.53T>A)?

AlphaMissense predicts likely pathogenic (score 0.833) — an in-silico prediction, not a clinical call.

DSPP p.Val18Asp

c.53T>A · rs1727745724 · VCV1320199

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
AlphaMissense	0.833	likely pathogenic ✓ concordant with ClinVar
REVEL	0.742	pathogenic-leaning
SaProt	LLR -10.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	24.8	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.Val18Asp
Coding: c.53T>A
dbSNP: rs1727745724
Type: single nucleotide variant
Location: chr4:87612106 (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-val18asp (accessed [today's date]).

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