Is DSPP p.1086DSS[1] (c.3264_3272del) pathogenic?

DSPP p.1086DSS[1] (c.32643272del) is classified Benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-10). Common (popmax 22.5%, amr) — too common for a highly-penetrant pathogenic allele.

DSPP p.1086DSS[1]

Q: How common is DSPP p.1086DSS[1] (c.3264_3272del) in the general population?

DSPP p.1086DSS[1] (c.3264_3272del) is common (popmax 22.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3264_3272del · rs367717407 · VCV1262686

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 22.5%, amr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -1.6
Overall
CADD	2.23	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GATAGCAGT simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.5% Admixed American · 5,187/23,008 alleles

Filtering AF 22% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.8%

Overall 16% 105,015/654,398 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	44.6%	2
Finnishnot grpmax-eligible	30.7%	3
Admixed Americangrpmax	22.5%	4
East Asian	22.1%	5
African / African-American	19.4%	5
Middle Eastern	18.8%	5
Remaining individualsnot grpmax-eligible	15.1%	7
European (non-Finnish)	15.1%	7
Ashkenazi Jewishnot grpmax-eligible	13.8%	7
South Asian	7.35%	14

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.1086DSS[1]
Coding: c.3264_3272del
dbSNP: rs367717407
Type: Deletion
Location: chr4:87615921 (GRCh38)

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

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-1086dss-1 (accessed [today's date]).

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