Is DSPP p.943DSS[2] (c.2838_2846del) pathogenic?

DSPP p.943DSS[2] (c.28382846del) is classified Benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-26). Common (popmax 6.43%, afr) — too common for a highly-penetrant pathogenic allele.

DSPP p.943DSS[2]

Q: How common is DSPP p.943DSS[2] (c.2838_2846del) in the general population?

DSPP p.943DSS[2] (c.2838_2846del) is common (popmax 6.43%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2838_2846del · rs751149319 · VCV1262516

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.43%, afr) — 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 -1.7
Overall
CADD	4.923	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	MLT1N2 ltr, simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.43% African / African-American · 4,677/72,772 alleles

Filtering AF 6.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.21%

Overall 0.338% 5,247/1,550,580 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.43%	16
Admixed American	0.515%	194
Remaining individualsnot grpmax-eligible	0.413%	242
Middle Eastern	0.0501%	1,995
South Asian	0.0167%	6,001
European (non-Finnish)	0.00375%	26,665

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.943DSS[2]
Coding: c.2838_2846del
dbSNP: rs751149319
Type: Deletion
Location: chr4:87615492 (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-943dss-2 (accessed [today's date]).

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