Is DSPP p.Ser1058= (c.3174T>C) pathogenic?

DSPP p.Ser1058= (c.3174T>C) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2014-10-15). Ultra-rare (popmax 0.086%, mid).

How common is DSPP p.Ser1058= (c.3174T>C) in the general population?

DSPP p.Ser1058= (c.3174T>C) is ultra-rare (popmax 0.086%, mid) (gnomAD).

DSPP p.Ser1058=

c.3174T>C · rs755899195 · VCV197811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.086%, mid)

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	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.086% Middle Eastern · 5/5,814 alleles

Filtering AF 0.0338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.022%

Overall 0.00189% 29/1,531,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.086%	1,163
Ashkenazi Jewishnot grpmax-eligible	0.0106%	9,437
African / African-American	0.00896%	11,160
Remaining individualsnot grpmax-eligible	0.00839%	11,923
East Asian	0.00251%	39,910
South Asian	0.0012%	83,002
European (non-Finnish)	0.000702%	142,466

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.Ser1058=
Coding: c.3174T>C
dbSNP: rs755899195
Type: single nucleotide variant
Location: chr4:87615836 (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-ser1058 (accessed [today's date]).

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