Is DSPP p.Ser1100= (c.3300C>T) pathogenic?

DSPP p.Ser1100= (c.3300C>T) is classified Benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). Common (popmax 63.8%, eas) — too common for a highly-penetrant pathogenic allele.

DSPP p.Ser1100=

Q: How common is DSPP p.Ser1100= (c.3300C>T) in the general population?

DSPP p.Ser1100= (c.3300C>T) is common (popmax 63.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3300C>T · rs369973717 · VCV1244519

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 63.8%, 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 -20	GERP -1.7
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.8% East Asian · 4,780/7,488 alleles

Filtering AF 62.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.7%

Overall 24.3% 82,909/341,256 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	66.9%	1
East Asiangrpmax	63.8%	2
Admixed American	47.3%	2
African / African-American	34.7%	3
Remaining individualsnot grpmax-eligible	30.8%	3
Amishnot grpmax-eligible	25.3%	4
European (non-Finnish)	20.6%	5
Ashkenazi Jewishnot grpmax-eligible	20%	5
Middle Eastern	16.7%	6
South Asian	16.5%	6

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.Ser1100=
Coding: c.3300C>T
dbSNP: rs369973717
Type: single nucleotide variant
Location: chr4:87615962 (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-ser1100 (accessed [today's date]).

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