Is DSPP p.Ser845= (c.2535C>T) pathogenic?

DSPP p.Ser845= (c.2535C>T) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-01). Low-frequency (popmax 1.31%, sas).

How common is DSPP p.Ser845= (c.2535C>T) in the general population?

DSPP p.Ser845= (c.2535C>T) is low-frequency (popmax 1.31%, sas) (gnomAD).

DSPP p.Ser845=

c.2535C>T · rs367568852 · VCV1208118

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, 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 -11	GERP -1.4
Overall
CADD	2.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% South Asian · 1,053/80,392 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.22%

Overall 0.127% 1,915/1,509,284 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.31%	76
African / African-American	0.78%	128
Remaining individualsnot grpmax-eligible	0.236%	424
Admixed American	0.0938%	1,066
Middle Eastern	0.0688%	1,453
European (non-Finnish)	0.0109%	9,194
Finnishnot grpmax-eligible	0.00175%	57,280

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.Ser845=
Coding: c.2535C>T
dbSNP: rs367568852
Type: single nucleotide variant
Location: chr4:87615197 (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-ser845 (accessed [today's date]).

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