Is DSPP p.Asn446= (c.1338T>C) pathogenic?

DSPP p.Asn446= (c.1338T>C) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-03-01). Rare (popmax 0.167%, afr).

How common is DSPP p.Asn446= (c.1338T>C) in the general population?

DSPP p.Asn446= (c.1338T>C) is rare (popmax 0.167%, afr) (gnomAD).

DSPP p.Asn446=

c.1338T>C · rs371567368 · VCV1202147

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, afr)

⚠ 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 -3.9	GERP -2.5
Overall
CADD	0.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% African / African-American · 125/74,884 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0088% 142/1,613,966 alleles · rare exomes 73/1,461,880 · genomes 69/152,086 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.167%	599
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00833%	12,001
South Asian	0.0011%	91,082
European (non-Finnish)	0.000424%	236,004

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.Asn446=
Coding: c.1338T>C
MANE Select: NM_014208
dbSNP: rs371567368
Type: single nucleotide variant
Location: chr4:87614000 (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-asn446 (accessed [today's date]).

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