Is DSPP p.Arg488Gln (c.1463G>A) pathogenic?

DSPP p.Arg488Gln (c.1463G>A) is classified Likely benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.0772); Very rare (popmax 0.00533%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Arg488Gln (c.1463G>A)?

DSPP p.Arg488Gln (c.1463G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Arg488Gln (c.1463G>A) in the general population?

DSPP p.Arg488Gln (c.1463G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about DSPP p.Arg488Gln (c.1463G>A)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

DSPP p.Arg488Gln

c.1463G>A · VCV4245144

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -3.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.015	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 0.00533% African / African-American · 4/75,062 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00186% 30/1,614,224 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,765
Admixed American	0.005%	20,009
East Asian	0.00223%	44,884
European (non-Finnish)	0.00178%	56,192
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Arg488Gln
Coding: c.1463G>A
Type: single nucleotide variant
Location: chr4:87614125 (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-arg488gln (accessed [today's date]).

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