Is DSPP p.Ser1067Arg (c.3201T>A) pathogenic?

DSPP p.Ser1067Arg (c.3201T>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.7359); Ultra-rare (popmax 0.0343%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1067Arg (c.3201T>A)?

DSPP p.Ser1067Arg (c.3201T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1067Arg (c.3201T>A) in the general population?

DSPP p.Ser1067Arg (c.3201T>A) is ultra-rare (popmax 0.0343%, mid) (gnomAD).

What do computational predictors say about DSPP p.Ser1067Arg (c.3201T>A)?

AlphaMissense predicts likely pathogenic (score 0.7359) — an in-silico prediction, not a clinical call.

DSPP p.Ser1067Arg

c.3201T>A · rs777438479 · VCV3085996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7359 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0343%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7359	likely pathogenic
REVEL	0.263	benign-leaning
SaProt	LLR -12.18	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 -2.1
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	8.606	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 0.0343% Middle Eastern · 2/5,828 alleles

Filtering AF 0.00819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00839% 117/1,393,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0343%	2,914
East Asian	0.0176%	5,677
Ashkenazi Jewishnot grpmax-eligible	0.0106%	9,431
Remaining individualsnot grpmax-eligible	0.0101%	9,929
Finnishnot grpmax-eligible	0.00863%	11,582
Admixed American	0.00811%	12,324
European (non-Finnish)	0.00737%	13,563
African / African-American	0.0045%	22,217
South Asian	0.00364%	27,485

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.Ser1067Arg
Coding: c.3201T>A
dbSNP: rs777438479
Type: single nucleotide variant
Location: chr4:87615863 (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-ser1067arg (accessed [today's date]).

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