Is DSPP p.Asp1146= (c.3438C>T) pathogenic?

DSPP p.Asp1146= (c.3438C>T) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-01). Very rare (popmax 0.00379%, sas).

How common is DSPP p.Asp1146= (c.3438C>T) in the general population?

DSPP p.Asp1146= (c.3438C>T) is very rare (popmax 0.00379%, sas) (gnomAD).

DSPP p.Asp1146=

c.3438C>T · rs746991642 · VCV2654917

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00379%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -1.8
Overall
CADD	0.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00379% South Asian · 3/79,100 alleles

Filtering AF 0.0012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00193% 29/1,503,652 alleles · very rare exomes 27/1,364,026 · genomes 2/139,626 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00379%	26,367
Finnishnot grpmax-eligible	0.00352%	28,411
East Asian	0.00284%	35,182
Admixed American	0.00211%	47,330
European (non-Finnish)	0.00186%	53,631
African / African-American	0.0015%	66,870

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.Asp1146=
Coding: c.3438C>T
MANE Select: NM_014208
dbSNP: rs746991642
Type: single nucleotide variant
Location: chr4:87616100 (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-asp1146 (accessed [today's date]).

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