Is DSPP p.Ser1160Cys (c.3478A>T) pathogenic?

DSPP p.Ser1160Cys (c.3478A>T) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: likely pathogenic (0.5838); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1160Cys (c.3478A>T)?

DSPP p.Ser1160Cys (c.3478A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1160Cys (c.3478A>T) in the general population?

DSPP p.Ser1160Cys (c.3478A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Ser1160Cys (c.3478A>T)?

AlphaMissense predicts likely pathogenic (score 0.5838) — an in-silico prediction, not a clinical call.

DSPP p.Ser1160Cys

c.3478A>T · VCV3842728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5838 · 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	0.5838	likely pathogenic
REVEL	0.222	benign-leaning
SaProt	LLR -13.33	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 3.9	GERP 1.2, phastCons 0.99
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	18.69	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.Ser1160Cys
Coding: c.3478A>T
Type: single nucleotide variant
Location: chr4:87616140 (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-ser1160cys (accessed [today's date]).

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