Is DSPP p.Asp975Asn (c.2923G>A) pathogenic?

DSPP p.Asp975Asn (c.2923G>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1151); Ultra-rare (popmax 0.0124%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp975Asn (c.2923G>A)?

DSPP p.Asp975Asn (c.2923G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp975Asn (c.2923G>A) in the general population?

DSPP p.Asp975Asn (c.2923G>A) is ultra-rare (popmax 0.0124%, eas) (gnomAD).

What do computational predictors say about DSPP p.Asp975Asn (c.2923G>A)?

AlphaMissense predicts likely benign (score 0.1151) — an in-silico prediction, not a clinical call.

DSPP p.Asp975Asn

c.2923G>A · VCV4245172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1151 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1151	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1	GERP -1.6
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	9.452	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0124% East Asian · 5/40,446 alleles

Filtering AF 0.00644% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00409% 63/1,541,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0124%	8,089
South Asian	0.012%	8,350
Remaining individualsnot grpmax-eligible	0.00668%	14,961
Admixed American	0.006%	16,657
European (non-Finnish)	0.00358%	27,911

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.Asp975Asn
Coding: c.2923G>A
Type: single nucleotide variant
Location: chr4:87615585 (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-asp975asn (accessed [today's date]).

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