Is DSPP p.Ser1169= (c.3507C>T) pathogenic?

DSPP p.Ser1169= (c.3507C>T) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-01). Ultra-rare (popmax 0.0122%, amr).

How common is DSPP p.Ser1169= (c.3507C>T) in the general population?

DSPP p.Ser1169= (c.3507C>T) is ultra-rare (popmax 0.0122%, amr) (gnomAD).

DSPP p.Ser1169=

c.3507C>T · rs201044279 · VCV2654923

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, amr)

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 -2.1
Overall
CADD	2.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0122% Admixed American · 6/49,048 alleles

Filtering AF 0.00589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00427%

Overall 0.00347% 53/1,527,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0122%	8,175
African / African-American	0.0119%	8,430
Remaining individualsnot grpmax-eligible	0.00508%	19,697
Ashkenazi Jewishnot grpmax-eligible	0.00358%	27,948
European (non-Finnish)	0.00281%	35,527
East Asian	0.00252%	39,704
Finnishnot grpmax-eligible	0.00173%	57,770
South Asian	0.00121%	82,622

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.Ser1169=
Coding: c.3507C>T
dbSNP: rs201044279
Type: single nucleotide variant
Location: chr4:87616169 (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-ser1169 (accessed [today's date]).

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