Is DSPP p.Ser794Arg (c.2382C>A) pathogenic?

DSPP p.Ser794Arg (c.2382C>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-01). AlphaMissense: likely pathogenic (0.6949); Rare (popmax 0.151%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser794Arg (c.2382C>A)?

DSPP p.Ser794Arg (c.2382C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser794Arg (c.2382C>A) in the general population?

DSPP p.Ser794Arg (c.2382C>A) is rare (popmax 0.151%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Ser794Arg (c.2382C>A)?

AlphaMissense predicts likely pathogenic (score 0.6949) — an in-silico prediction, not a clinical call.

DSPP p.Ser794Arg

c.2382C>A · rs189169726 · VCV2357241

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6949 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6949	likely pathogenic
REVEL	0.152	moderately benign-leaning
SaProt	LLR -11.07	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 -10	GERP -1.4
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	3.808	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 0.151% European (non-Finnish) · 1,731/1,146,538 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.119% 1,838/1,550,554 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.151%	662
Remaining individualsnot grpmax-eligible	0.0816%	1,226
Admixed American	0.0707%	1,414
African / African-American	0.022%	4,555
Middle Eastern	0.0168%	5,966
Finnishnot grpmax-eligible	0.00837%	11,952

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.Ser794Arg
Coding: c.2382C>A
dbSNP: rs189169726
Type: single nucleotide variant
Location: chr4:87615044 (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-ser794arg (accessed [today's date]).

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