Is DSPP p.Ser1084Asn (c.3251G>A) pathogenic?

DSPP p.Ser1084Asn (c.3251G>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.1767); Very rare (popmax 0.000272%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1084Asn (c.3251G>A)?

DSPP p.Ser1084Asn (c.3251G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1084Asn (c.3251G>A) in the general population?

DSPP p.Ser1084Asn (c.3251G>A) is very rare (popmax 0.000272%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Ser1084Asn (c.3251G>A)?

AlphaMissense predicts likely benign (score 0.1767) — an in-silico prediction, not a clinical call.

DSPP p.Ser1084Asn

c.3251G>A · rs1277112034 · VCV2525350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000272%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1767	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP 0.083, phastCons 0.37
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	13.69	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 0.000272% European (non-Finnish) · 2/735,702 alleles

Filtering AF 4.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7e-05%

Overall 0.000203% 2/985,788 alleles · very rare

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.Ser1084Asn
Coding: c.3251G>A
dbSNP: rs1277112034
Type: single nucleotide variant
Location: chr4:87615913 (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-ser1084asn (accessed [today's date]).

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