Is DSPP p.Ser1076Arg (c.3228C>A) pathogenic?

DSPP p.Ser1076Arg (c.3228C>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-25). AlphaMissense: likely pathogenic (0.6717); Ultra-rare (popmax 0.0179%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1076Arg (c.3228C>A)?

DSPP p.Ser1076Arg (c.3228C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1076Arg (c.3228C>A) in the general population?

DSPP p.Ser1076Arg (c.3228C>A) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about DSPP p.Ser1076Arg (c.3228C>A)?

AlphaMissense predicts likely pathogenic (score 0.6717) — an in-silico prediction, not a clinical call.

DSPP p.Ser1076Arg

c.3228C>A · rs1399473810 · VCV3086001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6717	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -12.01	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 -20	GERP -2.1
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	0.945	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 0.0179% East Asian · 7/39,048 alleles

Filtering AF 0.00832% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00596%

Overall 0.00491% 68/1,385,248 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,578
Middle Eastern	0.0175%	5,702
Finnishnot grpmax-eligible	0.0123%	8,118
Admixed American	0.0085%	11,770
South Asian	0.0074%	13,513
Ashkenazi Jewishnot grpmax-eligible	0.00708%	14,133
Remaining individualsnot grpmax-eligible	0.00681%	14,680
African / African-American	0.00349%	28,627
European (non-Finnish)	0.00308%	32,448

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.Ser1076Arg
Coding: c.3228C>A
dbSNP: rs1399473810
Type: single nucleotide variant
Location: chr4:87615890 (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-ser1076arg (accessed [today's date]).

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