Is DSPP p.Ser1112= (c.3336C>T) pathogenic?

DSPP p.Ser1112= (c.3336C>T) is classified Benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). Common (popmax 6.66%, eas) — too common for a highly-penetrant pathogenic allele.

DSPP p.Ser1112=

Q: How common is DSPP p.Ser1112= (c.3336C>T) in the general population?

DSPP p.Ser1112= (c.3336C>T) is common (popmax 6.66%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3336C>T · rs529175881 · VCV1271013

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.66%, eas) — too common for a highly-penetrant pathogenic allele

⚠ 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	3.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.66% East Asian · 982/14,740 alleles

Filtering AF 6.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.18%

Overall 2.84% 15,596/548,398 alleles · common exomes 14,788/525,744 · genomes 808/22,654 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	6.66%	15
Finnishnot grpmax-eligible	5.94%	17
Remaining individualsnot grpmax-eligible	3.37%	30
European (non-Finnish)	2.79%	36
Admixed American	2.41%	41
South Asian	1.97%	51
Ashkenazi Jewishnot grpmax-eligible	1.61%	62
Middle Eastern	1.24%	80
African / African-American	1.22%	82
Amishnot grpmax-eligible	0.84%	119

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.Ser1112=
Coding: c.3336C>T
MANE Select: NM_014208
dbSNP: rs529175881
Type: single nucleotide variant
Location: chr4:87615998 (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-ser1112 (accessed [today's date]).

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