Is DSPP p.Ser1045Arg (c.3135C>A) pathogenic?

DSPP p.Ser1045Arg (c.3135C>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely pathogenic (0.7875); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1045Arg (c.3135C>A)?

DSPP p.Ser1045Arg (c.3135C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1045Arg (c.3135C>A) in the general population?

DSPP p.Ser1045Arg (c.3135C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Ser1045Arg (c.3135C>A)?

AlphaMissense predicts likely pathogenic (score 0.7875) — an in-silico prediction, not a clinical call.

DSPP p.Ser1045Arg

c.3135C>A · rs1302769818 · VCV2556275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7875	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -11.61	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 -16	GERP -1.8
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	2.0	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.Ser1045Arg
Coding: c.3135C>A
dbSNP: rs1302769818
Type: single nucleotide variant
Location: chr4:87615797 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser1045arg (accessed [today's date]).

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