Is DSPP p.Asp632Asn (c.1894G>A) pathogenic?

DSPP p.Asp632Asn (c.1894G>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp632Asn (c.1894G>A)?

DSPP p.Asp632Asn (c.1894G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp632Asn (c.1894G>A) in the general population?

DSPP p.Asp632Asn (c.1894G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about DSPP p.Asp632Asn (c.1894G>A)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

DSPP p.Asp632Asn

c.1894G>A · VCV3505553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.6	GERP -1.9, phastCons 0.001
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	9.439	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,990 alleles

Filtering AF 0.0064% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00456%

Overall 0.00303% 47/1,550,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,990
Admixed American	0.0138%	7,270
African / African-American	0.00826%	12,101
Finnishnot grpmax-eligible	0.00503%	19,889
Remaining individualsnot grpmax-eligible	0.005%	20,014
East Asian	0.0049%	20,410
South Asian	0.00476%	20,991
European (non-Finnish)	0.00183%	54,595

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.Asp632Asn
Coding: c.1894G>A
Type: single nucleotide variant
Location: chr4:87614556 (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-asp632asn (accessed [today's date]).

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