Is DSPP p.Arg354= (c.1062C>T) pathogenic?

DSPP p.Arg354= (c.1062C>T) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00659%, sas).

How common is DSPP p.Arg354= (c.1062C>T) in the general population?

DSPP p.Arg354= (c.1062C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

DSPP p.Arg354=

c.1062C>T · rs751979983 · VCV1216499

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 0.59	GERP -2.6, phastCons 0.004
Overall
CADD	2.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,048 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.0013% 21/1,613,710 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,175
Admixed American	0.005%	20,000
East Asian	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000763%	131,110

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.Arg354=
Coding: c.1062C>T
dbSNP: rs751979983
Type: single nucleotide variant
Location: chr4:87613248 (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-arg354 (accessed [today's date]).

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