Is DSPP p.Ser1046= (c.3138C>T) pathogenic?

DSPP p.Ser1046= (c.3138C>T) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-09). Ultra-rare (popmax 0.0298%, afr).

How common is DSPP p.Ser1046= (c.3138C>T) in the general population?

DSPP p.Ser1046= (c.3138C>T) is ultra-rare (popmax 0.0298%, afr) (gnomAD).

DSPP p.Ser1046=

c.3138C>T · rs780332314 · VCV3024751

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0298%, afr)

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 -1.8
Overall
CADD	0.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0298% African / African-American · 18/60,316 alleles

Filtering AF 0.0193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.0128% 171/1,336,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0298%	3,351
South Asian	0.0248%	4,025
Middle Eastern	0.0196%	5,108
Remaining individualsnot grpmax-eligible	0.0171%	5,856
Admixed American	0.0137%	7,291
European (non-Finnish)	0.0117%	8,560
Ashkenazi Jewishnot grpmax-eligible	0.0117%	8,581
Finnishnot grpmax-eligible	0.00186%	53,896

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.Ser1046=
Coding: c.3138C>T
dbSNP: rs780332314
Type: single nucleotide variant
Location: chr4:87615800 (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-ser1046 (accessed [today's date]).

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