Is DSPP p.Ala15Val (c.44C>T) pathogenic?

DSPP p.Ala15Val (c.44C>T) is classified Pathogenic in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-03-09). AlphaMissense: ambiguous (0.4067); Absent from gnomAD v4.1; Associated with DSPP-related disorders.

What condition is associated with DSPP p.Ala15Val (c.44C>T)?

DSPP p.Ala15Val (c.44C>T) is associated with DSPP-related disorders, dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Ala15Val (c.44C>T) in the general population?

DSPP p.Ala15Val (c.44C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Ala15Val (c.44C>T)?

AlphaMissense predicts ambiguous (score 0.4067) — an in-silico prediction, not a clinical call.

DSPP p.Ala15Val

c.44C>T · rs121912989 · VCV16859

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DSPP-related disorders

Computational evidence

Protein change
AlphaMissense	0.4067	ambiguous
REVEL	0.459	indeterminate
SaProt	LLR -7.22	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	26.1	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.Ala15Val
Coding: c.44C>T
dbSNP: rs121912989
Type: single nucleotide variant
Location: chr4:87610952 (GRCh38)

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

Disease context

DSPP-related disorders

Also linked: dentinogenesis imperfecta type 2

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-ala15val (accessed [today's date]).

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