Is DSPP p.Ser1088= (c.3264T>C) pathogenic?

DSPP p.Ser1088= (c.3264T>C) is classified Likely benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Common (popmax 12.2%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1088= (c.3264T>C)?

DSPP p.Ser1088= (c.3264T>C) is associated with Inborn genetic diseases (ClinVar).

DSPP p.Ser1088=

Q: How common is DSPP p.Ser1088= (c.3264T>C) in the general population?

DSPP p.Ser1088= (c.3264T>C) is common (popmax 12.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3264T>C · rs373805744 · VCV3086018

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.2%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -5	GERP -1.6
Overall
CADD	1.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.2% Admixed American · 264/2,170 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.5%

Overall 2.7% 3,867/143,236 alleles · common exomes 3,530/138,190 · genomes 337/5,046 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	12.9%	8
Admixed Americangrpmax	12.2%	8
East Asian	11.2%	9
African / African-American	4.58%	22
South Asian	3%	33
Amishnot grpmax-eligible	2.73%	37
Remaining individualsnot grpmax-eligible	2.61%	38
Middle Eastern	2.53%	39
European (non-Finnish)	2.08%	48
Ashkenazi Jewishnot grpmax-eligible	1.68%	60

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.Ser1088=
Coding: c.3264T>C
MANE Select: NM_014208
dbSNP: rs373805744
Type: single nucleotide variant
Location: chr4:87615926 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser1088 (accessed [today's date]).

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