Is DSPP p.Asp1098= (c.3294T>C) pathogenic?

DSPP p.Asp1098= (c.3294T>C) is classified Benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). Common (popmax 51.5%, eas) — too common for a highly-penetrant pathogenic allele.

DSPP p.Asp1098=

Q: How common is DSPP p.Asp1098= (c.3294T>C) in the general population?

DSPP p.Asp1098= (c.3294T>C) is common (popmax 51.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3294T>C · rs531156875 · VCV1257816

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 51.5%, eas) — 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 -12	GERP -1.7
Overall
CADD	0.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.5% East Asian · 3,799/7,378 alleles

Filtering AF 50.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.6%

Overall 21.3% 70,779/331,664 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	63%	2
East Asiangrpmax	51.5%	2
Admixed American	42.9%	2
African / African-American	36.5%	3
Amishnot grpmax-eligible	30.3%	3
Remaining individualsnot grpmax-eligible	26%	4
Middle Eastern	19.9%	5
Ashkenazi Jewishnot grpmax-eligible	19.5%	5
European (non-Finnish)	17.7%	6
South Asian	12%	8

Finnish 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.Asp1098=
Coding: c.3294T>C
dbSNP: rs531156875
Type: single nucleotide variant
Location: chr4:87615956 (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-asp1098 (accessed [today's date]).

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