Is DSPP p.Ser1106= (c.3318C>T) pathogenic?

DSPP p.Ser1106= (c.3318C>T) is classified Benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Common (popmax 20.4%, eas) — too common for a highly-penetrant pathogenic allele.

DSPP p.Ser1106=

Q: How common is DSPP p.Ser1106= (c.3318C>T) in the general population?

DSPP p.Ser1106= (c.3318C>T) is common (popmax 20.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3318C>T · rs767275105 · VCV1249752

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 20.4%, 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 -2
Overall
CADD	1.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.4% East Asian · 3,005/14,752 alleles

Filtering AF 19.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.5%

Overall 8.89% 40,949/460,710 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	20.4%	5
Finnishnot grpmax-eligible	17.7%	6
Amishnot grpmax-eligible	17%	6
Remaining individualsnot grpmax-eligible	10.9%	9
European (non-Finnish)	8.33%	12
Admixed American	8.09%	12
Ashkenazi Jewishnot grpmax-eligible	7.09%	14
African / African-American	6.9%	15
Middle Eastern	5.77%	17
South Asian	5.67%	18

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.Ser1106=
Coding: c.3318C>T
dbSNP: rs767275105
Type: single nucleotide variant
Location: chr4:87615980 (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-ser1106 (accessed [today's date]).

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