Is DSPP p.Ser1088Arg (c.3264T>A) pathogenic?

DSPP p.Ser1088Arg (c.3264T>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely pathogenic (0.7799); Ultra-rare (popmax 0.0244%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1088Arg (c.3264T>A)?

DSPP p.Ser1088Arg (c.3264T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1088Arg (c.3264T>A) in the general population?

DSPP p.Ser1088Arg (c.3264T>A) is ultra-rare (popmax 0.0244%, sas) (gnomAD).

What do computational predictors say about DSPP p.Ser1088Arg (c.3264T>A)?

AlphaMissense predicts likely pathogenic (score 0.7799) — an in-silico prediction, not a clinical call.

DSPP p.Ser1088Arg

c.3264T>A · rs373805744 · VCV3086017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7799 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0244%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7799	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -11.82	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5	GERP -1.6
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	3.212	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0244% South Asian · 4/16,378 alleles

Filtering AF 0.00827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00502%

Overall 0.00359% 5/139,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0244%	4,095
European (non-Finnish)	0.00093%	107,510

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.Ser1088Arg
Coding: c.3264T>A
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-ser1088arg (accessed [today's date]).

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