Is DSPP p.Asn958= (c.2874T>C) pathogenic?

DSPP p.Asn958= (c.2874T>C) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-01). Ultra-rare (popmax 0.0407%, afr).

How common is DSPP p.Asn958= (c.2874T>C) in the general population?

DSPP p.Asn958= (c.2874T>C) is ultra-rare (popmax 0.0407%, afr) (gnomAD).

DSPP p.Asn958=

c.2874T>C · rs374607352 · VCV197804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0407%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -1.9
Overall
CADD	0.485	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0407% African / African-American · 27/66,280 alleles

Filtering AF 0.0287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00281% 43/1,530,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0407%	2,455
Admixed American	0.00204%	49,122
Remaining individualsnot grpmax-eligible	0.00168%	59,526
European (non-Finnish)	0.00123%	81,421

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.Asn958=
Coding: c.2874T>C
dbSNP: rs374607352
Type: single nucleotide variant
Location: chr4:87615536 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-asn958 (accessed [today's date]).

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