Is DSPP p.Ser1064Arg (c.3192C>A) pathogenic?

DSPP p.Ser1064Arg (c.3192C>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.7125); Very rare (popmax 0.00747%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1064Arg (c.3192C>A)?

DSPP p.Ser1064Arg (c.3192C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1064Arg (c.3192C>A) in the general population?

DSPP p.Ser1064Arg (c.3192C>A) is very rare (popmax 0.00747%, eas) (gnomAD).

What do computational predictors say about DSPP p.Ser1064Arg (c.3192C>A)?

AlphaMissense predicts likely pathogenic (score 0.7125) — an in-silico prediction, not a clinical call.

DSPP p.Ser1064Arg

c.3192C>A · VCV4245151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00747%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7125	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -12.20	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 -20	GERP -1.6
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	0.12	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 0.00747% East Asian · 3/40,172 alleles

Filtering AF 0.00198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00154%

Overall 0.00323% 45/1,394,452 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0102%	9,794
East Asiangrpmax	0.00747%	13,391
Ashkenazi Jewishnot grpmax-eligible	0.00704%	14,200
Remaining individualsnot grpmax-eligible	0.00503%	19,885
European (non-Finnish)	0.00254%	39,391
South Asian	0.00241%	41,413

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1064Arg
Coding: c.3192C>A
Type: single nucleotide variant
Location: chr4:87615854 (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-ser1064arg (accessed [today's date]).

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