Is DSPP p.Ser593Arg (c.1779T>G) pathogenic?

DSPP p.Ser593Arg (c.1779T>G) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely pathogenic (0.6661); Very rare (popmax 0.00375%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser593Arg (c.1779T>G)?

DSPP p.Ser593Arg (c.1779T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser593Arg (c.1779T>G) in the general population?

DSPP p.Ser593Arg (c.1779T>G) is very rare (popmax 0.00375%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Ser593Arg (c.1779T>G)?

AlphaMissense predicts likely pathogenic (score 0.6661) — an in-silico prediction, not a clinical call.

DSPP p.Ser593Arg

c.1779T>G · VCV4618022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00375%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6661	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -12.56	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 -5.4	GERP -0.38
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	8.595	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 0.00375% European (non-Finnish) · 43/1,145,962 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00251%

Overall 0.00297% 46/1,548,180 alleles · very rare exomes 44/1,399,534 · genomes 2/148,646 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00375%	26,650
Remaining individualsnot grpmax-eligible	0.00333%	30,002
African / African-American	0.00139%	71,714

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.Ser593Arg
Coding: c.1779T>G
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87614441 (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-ser593arg (accessed [today's date]).

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