Is DSPP p.Asp1203Glu (c.3609T>G) pathogenic?

DSPP p.Asp1203Glu (c.3609T>G) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely benign (0.2282); Very rare (popmax 0.00254%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp1203Glu (c.3609T>G)?

DSPP p.Asp1203Glu (c.3609T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp1203Glu (c.3609T>G) in the general population?

DSPP p.Asp1203Glu (c.3609T>G) is very rare (popmax 0.00254%, amr) (gnomAD).

What do computational predictors say about DSPP p.Asp1203Glu (c.3609T>G)?

AlphaMissense predicts likely benign (score 0.2282) — an in-silico prediction, not a clinical call.

DSPP p.Asp1203Glu

c.3609T>G · rs115597449 · VCV2524189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2282 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2282	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -3.1
Regional constraint	o/e 0.72	unconstrained · MANE · 391 bp · p 0.00018 · regional, not allelic
Overall
CADD	2.239	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 0.00254% Admixed American · 1/39,374 alleles

Filtering AF 7.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000358% 5/1,394,772 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00254%	39,374
African / African-American	0.00215%	46,568
European (non-Finnish)	0.000281%	355,949

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.Asp1203Glu
Coding: c.3609T>G
dbSNP: rs115597449
Type: single nucleotide variant
Location: chr4:87616271 (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-asp1203glu (accessed [today's date]).

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