Is DSPP p.Ser596del (c.1783AGT[1]) pathogenic?

DSPP p.Ser596del (c.1783AGT[1]) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-09-21). Ultra-rare (popmax 0.0451%, amr); Associated with DSPP-related disorder.

What condition is associated with DSPP p.Ser596del (c.1783AGT[1])?

DSPP p.Ser596del (c.1783AGT[1]) is associated with DSPP-related disorder (ClinVar).

How common is DSPP p.Ser596del (c.1783AGT[1]) in the general population?

DSPP p.Ser596del (c.1783AGT[1]) is ultra-rare (popmax 0.0451%, amr) (gnomAD).

DSPP p.Ser596del

c.1783AGT[1] · rs1437344619 · VCV2629367

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, amr)

Conditions

DSPP-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.8	GERP 0.86
Overall
CADD	1.622	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GATAGCAGTGACAGT simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0451% Admixed American · 23/50,986 alleles

Filtering AF 0.0308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00374% 58/1,551,768 alleles · ultra-rare exomes 40/1,400,998 · genomes 18/150,770 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0451%	2,217
Remaining individualsnot grpmax-eligible	0.00997%	10,029
South Asian	0.0095%	10,524
African / African-American	0.00413%	24,187
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,652
East Asian	0.00245%	40,768
European (non-Finnish)	0.00139%	71,723

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSPP
Protein: p.Ser596del
Coding: c.1783AGT[1]
MANE Select: NM_014208
dbSNP: rs1437344619
Type: Microsatellite
Location: chr4:87614444 (GRCh38)

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

Disease context

DSPP-related disorder

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-ser596del (accessed [today's date]).

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