Is DSPP p.Ser1018= (c.3054T>C) pathogenic?

DSPP p.Ser1018= (c.3054T>C) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). Ultra-rare (popmax 0.0558%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1018= (c.3054T>C)?

DSPP p.Ser1018= (c.3054T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1018= (c.3054T>C) in the general population?

DSPP p.Ser1018= (c.3054T>C) is ultra-rare (popmax 0.0558%, afr) (gnomAD).

DSPP p.Ser1018=

c.3054T>C · rs559965652 · VCV3085995

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0558%, afr)

Conditions

Inborn genetic diseases

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 -12	GERP -1.7
Overall
CADD	1.446	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0558% African / African-American · 35/62,678 alleles

Filtering AF 0.0412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0362%

Overall 0.0123% 182/1,484,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.126%	794
African / African-Americangrpmax	0.0558%	1,791
Admixed American	0.0535%	1,870
Middle Eastern	0.0367%	2,725
Remaining individualsnot grpmax-eligible	0.026%	3,851
Ashkenazi Jewishnot grpmax-eligible	0.0256%	3,909
South Asian	0.0253%	3,952
European (non-Finnish)	0.00686%	14,576

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1018=
Coding: c.3054T>C
dbSNP: rs559965652
Type: single nucleotide variant
Location: chr4:87615716 (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-ser1018 (accessed [today's date]).

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